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Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice.
Toxicol Lett. 2007 Mar 08; 169(2):95-108.TL

Abstract

Cadmium immunotoxicity in rodents is primarily characterized by marked thymic damage and splenomegaly. To understand the toxicity of Cd on lymphoid cells in vivo, a single dose of Cd as CdCl2 (1.8 mg/kg, i.p.) was administered to male BALB/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA, intranucleosomal DNA fragmentation) were assessed in thymic and splenic single cell suspensions, at various time intervals. Lowering of body weight gain and cellularity and a loss in cell viability was seen in the Cd treated mice. The earliest significant increase in ROS at 18 h, followed by mitochondrial membrane depolarization, caspase-3 activation and GSH depletion at 24h in spleen and later at 48 h in thymus, strongly implicate the possible involvement of ROS. A pronounced inhibition of cell proliferative response at 48 h and 72 h may also be linked to Cd induced apoptosis. The morphological alterations including thymic cortical cell depletion and an increase in red pulp with diminished white pulp in spleen were observed at 48 h and beyond. The splenic cells appeared more susceptible than thymus cells to the adverse effects of Cd. The present study, therefore, demonstrates potentiation of oxidative stress followed by mitochondrial-caspase dependent apoptotic pathway. This may, in part, be responsible for causing suppression of cell proliferative response, thymic atrophy and splenomegaly.

Authors+Show Affiliations

Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.Box 80, Lucknow 226001, India.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17267144

Citation

Pathak, Neelima, and Shashi Khandelwal. "Role of Oxidative Stress and Apoptosis in Cadmium Induced Thymic Atrophy and Splenomegaly in Mice." Toxicology Letters, vol. 169, no. 2, 2007, pp. 95-108.
Pathak N, Khandelwal S. Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicol Lett. 2007;169(2):95-108.
Pathak, N., & Khandelwal, S. (2007). Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicology Letters, 169(2), 95-108.
Pathak N, Khandelwal S. Role of Oxidative Stress and Apoptosis in Cadmium Induced Thymic Atrophy and Splenomegaly in Mice. Toxicol Lett. 2007 Mar 8;169(2):95-108. PubMed PMID: 17267144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. AU - Pathak,Neelima, AU - Khandelwal,Shashi, Y1 - 2007/01/05/ PY - 2006/11/15/received PY - 2006/12/11/revised PY - 2006/12/11/accepted PY - 2007/2/3/pubmed PY - 2007/5/4/medline PY - 2007/2/3/entrez SP - 95 EP - 108 JF - Toxicology letters JO - Toxicol Lett VL - 169 IS - 2 N2 - Cadmium immunotoxicity in rodents is primarily characterized by marked thymic damage and splenomegaly. To understand the toxicity of Cd on lymphoid cells in vivo, a single dose of Cd as CdCl2 (1.8 mg/kg, i.p.) was administered to male BALB/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA, intranucleosomal DNA fragmentation) were assessed in thymic and splenic single cell suspensions, at various time intervals. Lowering of body weight gain and cellularity and a loss in cell viability was seen in the Cd treated mice. The earliest significant increase in ROS at 18 h, followed by mitochondrial membrane depolarization, caspase-3 activation and GSH depletion at 24h in spleen and later at 48 h in thymus, strongly implicate the possible involvement of ROS. A pronounced inhibition of cell proliferative response at 48 h and 72 h may also be linked to Cd induced apoptosis. The morphological alterations including thymic cortical cell depletion and an increase in red pulp with diminished white pulp in spleen were observed at 48 h and beyond. The splenic cells appeared more susceptible than thymus cells to the adverse effects of Cd. The present study, therefore, demonstrates potentiation of oxidative stress followed by mitochondrial-caspase dependent apoptotic pathway. This may, in part, be responsible for causing suppression of cell proliferative response, thymic atrophy and splenomegaly. SN - 0378-4274 UR - https://www.unboundmedicine.com/medline/citation/17267144/Role_of_oxidative_stress_and_apoptosis_in_cadmium_induced_thymic_atrophy_and_splenomegaly_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(06)01386-5 DB - PRIME DP - Unbound Medicine ER -