Chronic kidney disease (CKD) is a worldwide health burden with increases risk of end-stage renal function if left untreated. CKD induced in the context of metabolic syndrome (MS) increases risks of hypertension, hyperglycemia, excess body fat and dyslipidemia. To test if combining a high-fat diet (HFD) regimen onto the hypertensive/ diabetic phenotype would mimic features of MS induced-CKD in mice, hyperglycemia was induced in genetically hypertensive mice (Lin), followed by HFD regimen. For that, 8-week-old male were subjected to streptozotocin (STZ) intraperitoneal (i.p.) injections (50 mg/kg, 5 days consecutive). LinSTZ were fed a 60% kCal HFD for 8 weeks. Lin mice treated with STZ developed polydipsia, became hypertensive and hyperglycemic. HFD induced weight gain, protected against glomerular hypertrophy, scarring, and albuminuria at endpoint compared to regular diet fed LinSTZ. On the other hand, HFD induced steatosis, liver fibrosis, inflammation, and increase in AST/ALT ratio, characteristics of non-alcoholic liver disease. Taken together, our results show that LinSTZ mice fed a HFD did not lead to a more robust model of MS-induced CKD, protected against kidney injury, but inducing liver damage. More studies are necessary to understand the kidney protective mechanisms of HFD when superimposed with hypertension and type 1 diabetes.

Cigarette smoke (CS) is a dominant carcinogenic agent in a variety of human cancers. CS exposure during pregnancy can adversely affect the fetus. Non-alcoholic fatty liver disease (NAFLD) is considered as a hepatic manifestation of a metabolic disorder, and ranges from simple steatosis to cirrhosis leading to hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a more severe phase of NAFLD. Recently, there is increasing apprehension about the CS-related chronic liver diseases. Therefore, we examined whether maternal CS exposure could affect the pathogenesis of NASH in offspring. Mainstream CS (MSCS) was exposed to pregnant C57BL/6 mice via nose-only inhalation for 2 h/day, 5 days/week for 2 weeks from day 6 to 17 of gestation at 0, 300, or 600 μg/L. Three-week-old male offspring mice were fed methionine and choline-supplemented (MCS) diet or methionine and choline-deficient including high-fat (MCDHF) diet for 6 weeks to induce NASH. Maternal MSCS exposure increased the severity of NASH by increasing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic total cholesterol (TC) and triglyceride (TG) levels, pro-inflammation, fibrosis, and steatosis in offspring mice. Especially, maternal MSCS exposure significantly downregulated the phosphorylation of AMP-activated protein kinase (AMPK) in MCDHF diet-fed offspring mice. Subsequently, the protein levels of sterol regulatory element-binding protein (SREBP)-1c and stearoyl-CoA desaturase-1 (SCD1) were upregulated by maternal MSCS exposure. In conclusion, maternal MSCS exposure exacerbates the progression of NASH by modulating lipogenesis on offspring mice.

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.

We studied the biochemical parameters of the blood of cattle after immunization against lumpy skin disease with a vaccine made from an attenuated heterologous goat pox virus (strain G20-LKV). Blood samples were obtained from animals on days 7, 14, and 21 after vaccination. The vaccine did not affect biochemical parameters of the blood. A slight increase in total protein and AST on day 14 indicates the expected reactions to the stimulation of the immune system after vaccination. The levels of direct and total bilirubin, ALT, urea, glucose, cholesterol, and creatinine in vaccinated animals remained within the physiological limits.

Consuming saline water causes animals salinity stress, which leads to many adapting metabolic changes that could negatively affect its performance and the quality of the derived products. Therefore, this study aimed to evaluate the impact of increasing diet protein level on the productive performance of growing lambs drinking natural saline water in Egyptian semi-arid region. Twenty-four growing Barki lambs (4-5 months old) with an initial body weight of 20.7 ± 0.25 kg were randomly distributed into four similar groups for 150 days. Two diets were formulated: low protein and high protein levels (concentrate feed mixture containing 14% and 20% crude protein (CP) on dry matter basis, respectively). Within each level of CP, natural saline water was represented by low saline (LS) and high saline (HS) water, containing 658 and 2100 mg/L of total dissolved solids, respectively. Results showed that the HS water increased (p = 0.02) water intake by about 18% and had adverse effect (p < 0.001) on dry matter intake, nutrient digestibility, and growth performance. The ruminal pH values, total volatile fatty acids, and ammonia-N concentrations were not affected by drinking the HS water. However, the protein supplementation enhanced the HS lambs' nutrients digestion and showed greater growth performance. The HS water decreased (p < 0.001) the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increased (p = 0.03) the urea-N by about 9%. The protein supplementation amended the serum ALT and AST concentrations of HS lambs. It is concluded that the dietary protein supply was affective sustainable management strategy against the deleterious effect of drinking high saline water on growing lambs.

Arsenic (As) can cause liver damage and liver cancer and is capable of seriously affecting human health. Therefore, it is important to identify biomarkers of arsenic-induced liver damage. Mitochondria are key targets of hepatotoxicity caused by arsenic. The mitochondrial DNA copy number (mtDNAcn) is the number of mitochondrial DNA (mtDNA) copies in the genome. mtDNA is vulnerable to exogenous chemical attacks, thus causing mtDNAcn to change after exposure to environmental pollutants. Therefore, mtDNAcn can serve as a potential marker to identify and assess the risk of diseases caused by exposure to environmental pollutants. In this study, we selected 272 arsenicosis patients (155 cases without liver damage and 117 cases with liver damage) and 218 participants not exposed to arsenic (155 cases without liver damage and 63 cases with liver damage) as subjects to investigate the correlation between peripheral blood mtDNAcn and arsenic-induced liver damage, as well as the ability of peripheral blood mtDNAcn to identify and assess the risk of arsenic-induced liver damage. Peripheral blood mtDNAcn in patients with arsenic-induced liver damage is significantly decreased and negatively correlated with serum ALT, AST, and GGT levels. The decrease of peripheral blood mtDNAcn was associated with an increased risk of arsenic-induced liver damage. The receiver operating characteristic (ROC) curve analysis indicated that peripheral blood mtDNAcn could specifically identify patients with liver damage in the arsenicosis group. The decision tree C5.0 model was established to identify arsenicosis in all patients with liver damage. Peripheral blood mtDNAcn was included in the model and played the most important role in the identification of arsenic-induced liver damage. This study provided a basis for the identification and evaluation of arsenic-induced liver damage by peripheral blood mtDNAcn, indicating that peripheral blood mtDNAcn is expected to be a potential biomarker of arsenic-induced liver damage, and provides clues for exploring the mechanism of arsenic-induced liver damage from mitochondria damage.

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Cadmium (Cd) accumulates in the body through contaminated foods or water and causes pathological damage to the liver via oxidative stress and inflammatory reactions. This study was conducted to explore the effects of dendropanoxide (DPx) on Cd-induced hepatotoxicity in rats. Sprague-Dawley (SD) rats were injected with CdCl2 (7 mg/kg body weight) intraperitoneally for 14 days for the induction of liver dysfunction. The CdCl2-exposed rats were subjected to DPx (10 mg/kg) or silymarin (50 mg/kg). The animals were euthanized after 24 h of the last CdCl2 injection and the serum biochemical parameters, lipid content, pro-inflammatory cytokine levels, apoptotic cell death and histopathology of the tissues were analyzed. Additionally, the activity of antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), was measured. Compared to controls, Cd-injected rats showed significantly elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol, and pro-inflammatory cytokines, and a remarkable decrease in SOD and CAT activities. Importantly, Cd-induced liver damage was drastically ameliorated by treatment with DPx or silymarin. Treatment with DPx protected the Cd-induced histopathological hepatic injury, as confirmed by the evaluation of TUNEL assay. DPx treatment significantly reduced Bax and caspase-3 expression in Cd-injected rats. Additionally, HO-1 and NRF2 expressions were significantly increased after DPx administration in the liver of Cd-injected rats. Our data indicate that DPx successfully prevents Cd-induced hepatotoxicity by emphasizing the antioxidant and anti-inflammatory effect.

InP/ZnS quantum dots (QDs) are widely used in biomedical imaging and light-emitting component manufacturing industries, but there are few studies on their biological toxicity. In this study, we conducted experiments with rare minnow larvae and found that InP/ZnS QDs can cause liver damage. InP/ZnS QDs appeared only in the intestine of larvae and were not enriched in other parts of the larvae. The activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) increased, while the decrease in bile acid. InP/ZnS QDs caused hepatic cell nuclear lysis, abnormal cytoplasmic staining, and mitochondrial cristae reduction, swelling, and fragmentation. RNA-sequencing results revealed that InP/ZnS QDs exposure treatment affected the expression of genes involved in lipid metabolism, sterol synthesis, bile acid synthesis and other pathways. The excessive production of reactive oxygen species (ROS) induced by InP/ZnS QDs may be the main source of toxicity.

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride (DG), which may be due to a decrease in the levels of phosphoethanolamine cytidyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase (PISD) pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with cytidine-5'-diphosphate-ethanolamine (CDP-etn) to increase the production of PE from the CDP-ethanolamine pathway reversed HG&FFA-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the PISD pathway, did not. Additionally, we found that overexpression of Pcyt2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and Pcyt2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and Pcyt2 overexpression ameliorate partial mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.

Steatosis is regarded as an early response of the liver to excessive alcohol consumption, which ultimately results in alcoholic liver disease (ALD). Hepatocytes are the primary drivers of the pathological process known as hepatic damage and steatosis, which is characterized by significant fat accumulation and an abundance of fat vacuoles. NLRs, a family member of pattern recognition receptors, have recently been found to be crucial in liver disorders. In this study, we examined the possible impact of NLRC5, the largest NLR family member, on alcohol-induced fatty liver development using a gene knock-out mouse model. The mouse liver was severely damaged and developed steatosis as a result of chronic and excessive ethanol use, and this damage was prevented by the lack of NLRC5. Additionally, NLRC5 deletion reversed ethanol's ability to increase the serum concentrations of TG, T-CHO, ALT, and AST. Absence of NLRC5 reduced ethanol-stimulated aberrant expression of the vital regulators of lipid synthesis and metabolism, SREBP-1c, FAS and PPAR-α. Furthermore, loss- and gain-of-function research indicated that NLRC5 might affect the autophagy pathway in alcohol-induced hepatic steatosis progression. The functional role of NLRC5 in ALD is obviously impacted by the autophagy inducer rapamycin as well as the autophagy inhibitor 3-MA. Our research showed that NLRC5 was involved in ethanol-induced injury and steatosis of the liver, and may be considered a suitable therapeutic target for treating ALD.

Studies have shown that exposure to air pollutants such as diesel exhaust particles (DEP) exacerbate diabetes complications. Morin hydrate (MH), a plant bioflavonoid, provides hepatoprotection due to its diverse pharmacological properties. This study examines the hepatoprotective effects of MH in Wistar rats with type 2 diabetes exposed to diesel exhaust (DE). Procured male Wistar rats (n = 60) were separated into 12 groups of five rat each. Type 2 diabetes was induced following oral therapy with fructose solution and one-time injection of 45 mg/kg of streptozotocin (STZ). The DEP extract was administered by nasal instillation, whereas MH was administered via oral gavage. Biochemical assays were used to determine the effect of MH on diabetic rats and DEP-exposed diabetic rats with respect to liver function indices (AST and ALT), liver antioxidants (SOD, CAT, Gpx, and GSH), lipid profile, and oxidative stress marker (conjugated diene and lipid peroxidation). The mRNA expression of PI3K/AKT/GLUT4 and AMPK/GLUT4 signaling pathways were quantified using RT-PCR. The results show that normal rats, diabetic rats, and diabetic rats exposed to DEP exhibited a substantial decrease in oxidative stress indicators, serum lipid profile, and levels of AST and ALP, as well as an increase in liver natural antioxidants following oral administration of MH. The gene expression study demonstrated that MH promotes the activation of the insulin signaling pathways which facilitates the uptake of glucose from the blood. This study suggests that MH offered hepatoprotection in type 2 diabetic rats and DEP exposed diabetic rats.

Profenofos (organophosphate) is among the major toxicant polluting freshwater bodies, exerting a significant effect on fish health. The LC50 value of Profenofos (PRO) was resolved in Grass carp (Ctenopharyngodon idella) with average body weight (55.82 ± 5.42 g) and determined the 96 h LC50 value as 7.2 µg/L for the assay. Twenty-one-day exposures to 1.8 µg/ L and 3.6 µg/ L doses were conducted to evaluate the sub-lethal effects, and various toxicological endpoints were assessed on the 1st, 7th, 15th and 21st days of exposure. Acute toxic stress was observed with fish displaying behavioral toxicity. The most hematological change was extreme microcytic hypochromic anemia. Leucocyte count increased in experimented fish. Moderate neutrophilia, monocytosis and lymphocytosis were observed. Serum total protein, albumin, and globulin concentrations were significantly diminished. Overall, increments over control were recognized in serum urea, creatinine and acid phosphatase. However, serum glucose, total lipid, cholesterol, serum ALT and AST activity showed a significant decrease in fish exposed to both concentrations of PRO. Serum IgM concentrations insignificantly changed in treated fish except for on the 21st day of exposure to 3.6 µg/ L of PRO, while serum lysozyme significantly decreased. Furthermore, total protein, lipid and glycogen concentrations in muscles and the liver exhibited a decreasing trend at all concentrations. Moreover, histopathological alterations in the liver, kidney, and muscles occurred exclusively after treatment. From the obtained results, it is assumed that profenofos induced general toxic impacts under field conditions and might disturb ecologically relevant processes.

To observe the metabolic changes and antialcoholic effect of Puerarin-PLGA nanoparticles (PUE-NP) in mice. PUE-NP was prepared and characterized by particle size distribution and morphology. The mouse models with acute alcoholism were established to observe their behavioral changes after alcohol poisoning. The expressions of biologically active enzymes such as CRE, BUN, AST, ALT in serum and SOD and TLR4 in liver of mice in each group were detected, and the pathological changes in liver and kidney tissues were observed by HE staining. The PUE-NP metabolism in mice was determined by in vitro release assay and HPLC. PUE-NP nanoparticles had good morphology and structure, and the mouse models with alcohol poisoning were established successfully. Compared with alcohol group, puerarin and PUE-NP increased the disappearance latency time of righting reflex, and the recovery time of righting reflex was significantly shortened. Water maze results showed that Puerarin and PUE-NP had inhibitory effect on impaired memory. HPLC results showed that PUE-NP reached its peak in mice after 1 h, and the content percentage was twice that of puerarin preparation alone, and the distribution time of puerarin concentration in vivo was prolonged, indicating that PLGA nanoparticles had a loading and slow-release effect on puerarin and increased the bioavailability of puerarin in mice. In addition, compared with the alcohol group, Puerarin and PUE-NP improved serum ALT, AST, CRE, and BUN levels in mice, enhanced SOD activity in liver, and inhibited TLR4 expression. The effect was better in the PUE-NP group than in the Puerarin group. PUE-NP delayed the release and metabolism of Puerarin and had better effect in the treatment of the alcoholic liver and kidney injury.

This study investigated the effect of heat stress on the physiological parameters, oxidation resistance ability and immune responses in juvenile hybrid yellow catfish. Heat stress group exposed to 35 °C and control to 28 °C. Blood and liver were sampled at different hours' post-exposure. Results showed that red blood cell (RBC), white blood cell (WBC) counts, Hemoglobin (HGB) levels and hematocrit (HCT) values increased significantly (P < 0.05) post-exposure to heat stress. This indicates the increase of cell metabolism. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), total protein (TP), triglyceride (TG) and glucose increased significantly (P < 0.05) indicating the need to cope with stress and cell damage. Liver TC, TG, COR hormone, C3 complement increased significantly from 24 to 96 h. Heat stress mostly affects the hepatic antioxidant and immune resistance functions, resulting in increments of cortisol levels, lysozyme, superoxide dismutase (SOD), and catalase (CAT) enzyme activities. The increase of Malondialdehyde (MDA), alkaline phosphatase (AKP) indicate stimulation of the immune responses to protect the liver cells from damage. The decrease in Liver TP indicated liver impairment. Decrease in Glycogen content from 6 to 96 h indicated mobilization of more metabolites to cope with increased energy demand. Interestingly, results showed that heat stress trigged costly responses in the experimental fish like accelerated metabolism and deplete energy reserves, which could indirectly affect ability of fish to set up efficient long term defense responses against stress. These results provide insight into prevention and management of stress in juvenile hybrid yellow catfish.

Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups - (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1β and TGF-β3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.

Malnutrition and low dietary protein intake could be risk factors for developing peripheral and central hyperammonemia, especially in pediatrics. Both curcumin and resveratrol proved to be effective against several hepatic and cerebral injuries. They were reported to be beneficial in lowering circulating ammonia levels, yet both are known for their low bioavailability. The use of pharmaceutical nano-formulations as delivery systems for these two nutraceuticals could solve the aforementioned problem. Hence, the present study aimed to investigate the valuable outcome of using a combination of curcumin and resveratrol in a nanoemulsion formulation, to counteract protein-deficient diet (PDD)-induced hyperammonemia and the consequent complications in male albino rats. Results revealed that using a nanoemulsion containing both curcumin and resveratrol at a dose of (5 + 5 mg/kg) effectively reduced hepatic and brain ammonia levels, serum ALT and AST levels, hepatic and brain nitric oxide levels, oxidative DNA damage as well as disrupted cellular energy performance. In addition, there was a substantial increase in brain levels of monoamines, and a decrease in glutamate content. Therefore, it can be concluded that the use of combined curcumin and resveratrol nanoemulsion is an effective means of ameliorating the hepatic and cerebral adverse effects resulting from PDD-induced hyperammonemia in rats.