臨床および実験薬理学ジャーナル

概要

The effect of Tamoxifen on Indomethacin induced hepato-nephrotoxicity in rats

Malak M Eljafari, Aisha M Dugani, Soad A Treesh, Amal Musa

Background: Indomethacin is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) with a known hepato-renal toxicity. Tamoxifen is the treatment of choice for women with estrogen receptor-positive breast cancer.

Aim: This study was aimed to investigate the effects of tamoxifen (TAM) on renal toxicity and hepatic damage induced by indomethacin (IND) in rats.

Methods: Hepato-renal toxicity was induced in female Wistar rats by a single dose of IND (150 mg/kg) administered by gavage. TAM pretreatment involved Subcutaneous (SC) administration of the drug in a dose of 0.5 mg/kg/day for 5 consecutive days. Assessment of liver and kidney toxicities was based on determination of the activity of liver enzymes sGPT, sGOT, ALP, serum urea and serum creatinine as well as the ratio of liver and kidneys weight to total body weight and on histopathological evaluation.

Results: Oral administration of IND produced a significant elevation in liver and kidneys weight ratio, sGOT, sGPT, serum urea and serum creatinine levels compared to negative control group. The pretreatment with TAM 0.5mg/kg before induction of IND toxicity, resulted in significant reduction in serum urea, creatinine and liver enzymes activity and significantly protected the liver and the kidneys from injury induced by IND. Histopathological examination of kidneys and livers confirmed the protective effect of TMA. This protection by TAM may be related to its scavenging activity of free radicals, its antioxidant properties or to stimulation of ERs by TAM and its metabolites.

Conclusion: This study may suggest that the pretreatment with multiple low doses of TAM will significantly reduce INDinduced hepato-renal toxicity.