Time response of carboplatin-induced nephrotoxicity in rats. Export

@article{citeulike:964164, abstract = {Carboplatin, a second-generation platinum-containing anti-cancer drug, is currently being used against human cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. We have shown a dose-dependent nephrotoxicity of carboplatin in a rat model. However, the time response of carboplatin-induced renal injury has not been explored. This study investigated the time response of carboplatin-induced nephrotoxicity in rat. Male Wistar rats (250-300 g) were divided into two groups of 30 animals each and treated as follows: (1) control (saline, intraperitoneally) and (2) carboplatin (256 mg kg(-1), intraperitoneally). The animals (n = 6) from each group were sacrificed 1-5 days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine, blood urea nitrogen (BUN), and blood urea levels were increased significantly in response to carboplatin in a time-dependent manner, indicating potential nephrotoxicity. Carboplatin time-dependently increased the renal platinum concentration, renal xanthine oxidase activity, increased membrane lipid peroxidation (MDA) concentration, while ratio of reduced-to-oxidized glutathione (GSH/GSSG) depleted significantly, indicating oxidative renal injury. Renal anti-oxidant enzymes, such as cytosolic copper/zinc-superoxide dismutase (CuZn-SOD) and mitochondrial manganese (Mn)-SOD, catalase (CAT), and glutathione peroxidase (GSH-Px) activities were decreased significantly due to carboplatin 3-5 days post-treatment. The protein expressions of renal CuZn-SOD and Mn-SOD significantly depleted 3-5 days after carboplatin administration, indicating decline in de novo synthesis of enzyme proteins. The data suggested that carboplatin caused time-dependent oxidative renal injury, as evidenced by renal anti-oxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine BUN, and blood urea levels in rats.}, address = {Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA. khusain@psm.edu}, author = {Husain, K. and Whitworth, C. and Rybak, L. P.}, citeulike-article-id = {964164}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.phrs.2004.04.001}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15225673}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15225673}, doi = {10.1016/j.phrs.2004.04.001}, issn = {1043-6618}, journal = {Pharmacol Res}, keywords = {carboplatinum}, month = {September}, number = {3}, pages = {291--300}, posted-at = {2006-11-27 21:21:58}, priority = {2}, title = {Time response of carboplatin-induced nephrotoxicity in rats.}, url = {http://dx.doi.org/10.1016/j.phrs.2004.04.001}, volume = {50}, year = {2004} }

TY - JOUR ID - citeulike:964164 L3 - citeulike-article-id:964164 N2 - Carboplatin, a second-generation platinum-containing anti-cancer drug, is currently being used against human cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. We have shown a dose-dependent nephrotoxicity of carboplatin in a rat model. However, the time response of carboplatin-induced renal injury has not been explored. This study investigated the time response of carboplatin-induced nephrotoxicity in rat. Male Wistar rats (250-300 g) were divided into two groups of 30 animals each and treated as follows: (1) control (saline, intraperitoneally) and (2) carboplatin (256 mg kg(-1), intraperitoneally). The animals (n = 6) from each group were sacrificed 1-5 days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine, blood urea nitrogen (BUN), and blood urea levels were increased significantly in response to carboplatin in a time-dependent manner, indicating potential nephrotoxicity. Carboplatin time-dependently increased the renal platinum concentration, renal xanthine oxidase activity, increased membrane lipid peroxidation (MDA) concentration, while ratio of reduced-to-oxidized glutathione (GSH/GSSG) depleted significantly, indicating oxidative renal injury. Renal anti-oxidant enzymes, such as cytosolic copper/zinc-superoxide dismutase (CuZn-SOD) and mitochondrial manganese (Mn)-SOD, catalase (CAT), and glutathione peroxidase (GSH-Px) activities were decreased significantly due to carboplatin 3-5 days post-treatment. The protein expressions of renal CuZn-SOD and Mn-SOD significantly depleted 3-5 days after carboplatin administration, indicating decline in de novo synthesis of enzyme proteins. The data suggested that carboplatin caused time-dependent oxidative renal injury, as evidenced by renal anti-oxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine BUN, and blood urea levels in rats. IS - 3 JF - Pharmacol Res SN - 1043-6618 AD - Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA. khusain@psm.edu EP - 300 TI - Time response of carboplatin-induced nephrotoxicity in rats. VL - 50 SP - 291 KW - carboplatinum AU - Husain, K AU - Whitworth, C AU - Rybak, LP PY - 2004/09// UR - http://dx.doi.org/10.1016/j.phrs.2004.04.001 ER -