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Diacerein ameliorates induced polycystic ovary in female rats via modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways.
Naunyn Schmiedebergs Arch Pharmacol. 2022 03; 395(3):295-304.NS

Abstract

Polycystic ovary syndrome (PCOS) is a very common gynecological disease during childbearing period and markedly affects female fertility. Until now, there are no studies evaluating the possible curative effect of diacerein (DIA) in induced PCOS. For the first time, we aimed in current model to study the effect of DIA (50 mg/kg/day) orally for 3 weeks on experimentally induced PCOS by letrozole (1 mg/kg/day) for 3 weeks. We measured rats' body weight changes, levels of serum insulin, anti-Müllerian hormone (AMH), testosterone, inflammasome, caspase1, and total anti-oxidant capacity (TAC). Moreover, we measured ovarian tissue parameters as malondialdehyde (MDA), interleukin 1β (IL1β), real-time polymerase chain reaction (rt-PCR) of Bcl2-associated X protein (Bax), and interleukin 10 (IL10) gene expression changes. Furthermore, histopathological features and anti-apoptotic marker B cell lymphoma 2 (Bcl2) immunoexpression changes were evaluated. Our results showed that letrozole markedly induced PCOS as manifested by significant increase in serum testosterone, insulin, AMH, rats' body weights, ovarian tissue MDA, IL1β, inflammasome, and caspase1 but decrease of serum TAC. In addition, gene expression of Bax increased but IL10 gene expression decreased. Ovaries showed the typical histopathological changes of PCOS with no immunoexpression of Bcl2. DIA was greatly able to ameliorate letrozole-induced PCOS changes in rats mainly via prevention of IL1β, and improving metabolic disturbances, and its anti-apoptotic, anti-oxidant, and anti-inflammatory effects with further regulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt. marwamonier@mu.edu.eg.Department of Pathology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt.Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34994825

Citation

Refaie, Marwa M M., et al. "Diacerein Ameliorates Induced Polycystic Ovary in Female Rats Via Modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 Pathways." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 395, no. 3, 2022, pp. 295-304.
Refaie MMM, El-Hussieny M, Abdelraheem WM. Diacerein ameliorates induced polycystic ovary in female rats via modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(3):295-304.
Refaie, M. M. M., El-Hussieny, M., & Abdelraheem, W. M. (2022). Diacerein ameliorates induced polycystic ovary in female rats via modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways. Naunyn-Schmiedeberg's Archives of Pharmacology, 395(3), 295-304. https://doi.org/10.1007/s00210-021-02175-2
Refaie MMM, El-Hussieny M, Abdelraheem WM. Diacerein Ameliorates Induced Polycystic Ovary in Female Rats Via Modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 Pathways. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(3):295-304. PubMed PMID: 34994825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diacerein ameliorates induced polycystic ovary in female rats via modulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways. AU - Refaie,Marwa M M, AU - El-Hussieny,Maram, AU - Abdelraheem,Wedad M, Y1 - 2022/01/07/ PY - 2021/05/27/received PY - 2021/10/28/accepted PY - 2022/1/8/pubmed PY - 2022/3/11/medline PY - 2022/1/7/entrez KW - Anti-Müllerian hormone KW - Diacerein KW - Insulin resistance KW - Interleukin 1β KW - Polycystic ovary syndrome SP - 295 EP - 304 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 395 IS - 3 N2 - Polycystic ovary syndrome (PCOS) is a very common gynecological disease during childbearing period and markedly affects female fertility. Until now, there are no studies evaluating the possible curative effect of diacerein (DIA) in induced PCOS. For the first time, we aimed in current model to study the effect of DIA (50 mg/kg/day) orally for 3 weeks on experimentally induced PCOS by letrozole (1 mg/kg/day) for 3 weeks. We measured rats' body weight changes, levels of serum insulin, anti-Müllerian hormone (AMH), testosterone, inflammasome, caspase1, and total anti-oxidant capacity (TAC). Moreover, we measured ovarian tissue parameters as malondialdehyde (MDA), interleukin 1β (IL1β), real-time polymerase chain reaction (rt-PCR) of Bcl2-associated X protein (Bax), and interleukin 10 (IL10) gene expression changes. Furthermore, histopathological features and anti-apoptotic marker B cell lymphoma 2 (Bcl2) immunoexpression changes were evaluated. Our results showed that letrozole markedly induced PCOS as manifested by significant increase in serum testosterone, insulin, AMH, rats' body weights, ovarian tissue MDA, IL1β, inflammasome, and caspase1 but decrease of serum TAC. In addition, gene expression of Bax increased but IL10 gene expression decreased. Ovaries showed the typical histopathological changes of PCOS with no immunoexpression of Bcl2. DIA was greatly able to ameliorate letrozole-induced PCOS changes in rats mainly via prevention of IL1β, and improving metabolic disturbances, and its anti-apoptotic, anti-oxidant, and anti-inflammatory effects with further regulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/34994825/Diacerein_ameliorates_induced_polycystic_ovary_in_female_rats_via_modulation_of_inflammasome/caspase1/IL1β_and_Bax/Bcl2_pathways_ L2 - https://dx.doi.org/10.1007/s00210-021-02175-2 DB - PRIME DP - Unbound Medicine ER -