Nephrotoxicity as a cause of death in male wistar rats exposed to toxic doses of paracetamol\methionine combination

Abstract

In an earlier study, we observed that male Wistar rats administered with

toxic doses of methionine containing paracetamol formulation

(acetaminophen) did not manifest hepatic necrosis even at doses as high as

3000 mg\kg and 5000 mg\kg body weight (BW) yet death occurred. This

study sets out to investigate the cause of death by focusing on another sensitive

organ to acetaminophen exposure and to highlight the role of some vitamins

in this. Thirty male Wistar rats were divided into six groups consisting 5

rats in each, and further administered with different doses of paracetamol\

methionine, ranging from 100 mg\kg – 5000 mg\kg. 5 rats, supplied

with only physiologic saline were considered as control. Results show that

rats exposed to 100mg\kg, 350 mg\kg and 1000 mg\kg BW did not exhibit

any form of renal abnormality. The nephrotoxic indices consisting of urea,

creatinine and uric acid were not significantly increased in comparison to

control (p>0.05). Renal histology was also not identified as abnormal; moreover

0% mortality was recorded for these groups. However, the creatinine

was significantly increased in 3000 mg\kg group (p<0.05). Histologically, mild

to severe renal tubular necrosis was observed among the rats exposed to

5000 mg\kg BW level of acetaminophen which suffered 100% mortality.

Thus, the acute renal failure may be a cause of death of Wistar rats exposed

to higher doses. Probably, as the results suggest that generation of other

reactive species that could not be detoxified by glutathione or inadequate

glutathione synthesis in the renal cells might have been the cause of death at

these high levels of exposure.