Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice.
Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneficial effect of 2-mercaptoethane sulphonate (MESNA), an antioxidant agent, against acetaminophen toxicity in mice. Balb-c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg(-1) MESNA (MES group); a single dose of 900 mg kg(-1) i.p. acetaminophen (AA4h and AA24h groups); and MESNA, at a dose of 150 mg kg(-1) after acetaminophen injection (AA4h-MES and AA24h-MES groups). The MESNA injection was repeated once more 12 h after the first injection in the AA24h-MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically. Blood urea nitrogen and serum creatinine, which were increased significantly (P < 0.001) following acetaminophen treatment were decreased significantly (P < 0.05-0.001) after treatment with MESNA. The ALT and AST levels were also increased significantly (P < 0.001) after acetaminophen treatment but were not reduced with MESNA. Acetaminophen treatment caused a significant (P < 0.05-0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by MESNA treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with MESNA. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that MESNA, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a 'tissue injury-limiting agent' must be elucidated further in drug-induced oxidative damage.
Sener
Göksel
G
School of Pharmacy, Department of Pharmacology, Marmara University, Istanbul, Turkey. gokselsener@hotmail.com
Sehirli
Ozer
O
Cetinel
Sule
S
Yeğen
Berrak G
BG
Gedik
Nursal
N
Ayanoğlu-Dülger
Gül
G
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D001806:Blood Urea Nitrogen; D003094:Collagen / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005260:Female; D005978:Glutathione / Q000032:analysis; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D007677:Kidney Function Tests; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D015080:Mesna / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D020011:Protective Agents; D000082:Acetaminophen; D008315:Malondialdehyde; D003094:Collagen; D003404:Creatinine; D009195:Peroxidase; D005978:Glutathione; D015080:Mesna