Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

Abstract

MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity.

Hepatotoxicity; Protective Effect of Silymarin Against Methotrexate Induced in Mice

“…It may be because of the single dose of MTX along with early sample collection. The findings are consistent with the Akbulut et al 13 and Tag 8 who also demonstrated elevation of LFTs in experimental rodents treated with MTX in same dose and route of administration. The exact pathogenesis of MTX induced hepatotoxicity is still unclear though different mechanisms are thought to participate in causing liver damage like accumulation of polyglutamates in hepatocytes, depletion of hepatic folate store resulting in decrease nucleic acid synthesis, inhibition of methionine biosynthesis and resultant increased homocysteine leading to increase cellular sensitization to reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with lipid peroxidation of biological membranes and microvascular derangement.…”

The effects of lycopene on methotrexate-induced liver injury in rats

“…Lyc, a powerful anti-oxidant, has been showed to be effective in reducing the nephrotoxicity caused by cisplatin, via decreasing oxidative stress (4,(38)(39)(40). Lyc's also has anti-infl ammatory and anti-cancer properties.The studies showed that it may be effective in reducing organ toxicity such as pancreas, testis and kidney (39,(41)(42)(43).…”

“…Therefore, several anti-oxidant agents have been used to reduce its side effects (10). Akbulut et al demonstrated the cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against Mtx-induced hepatotoxicity in rats (4). In addition, it has been reported that proinfl ammatory cytokines are involved in the pathogenesis of Mtx-induced nephrotoxicity and pneumonitis, suggesting that infl ammation may also have a possible role in Mtx-induced hepatotoxicity (11)(12)(13)(14)(15)(16).…”

“…Its cytotoxic characteristic causes some life-threatening adverse effects. One of the most serious side effect is hepatotoxicity, limiting the use of this agent (1)(2)(3)(4)(5). The mechanism of Mtx-induced hepatotoxicity has not been fully understood yet (6,7).…”

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

“…The animals in the experimental groups were administered an intraperitoneal daily dose of a specific substance, depending on the group, and the control group received the same quantity of 0.9% sodium chloride solution daily (35) according to the following protocol: a) control group (0.9% sodium chloride 0.1-0.2 ml/day) (n=10); b) methionine (0.8 mmol/kg/bw/day) (n=10) (MET group); c) methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n=8) (L-cys+MET group) (36); and d) methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n=8) (NAC+MET group) (37). Prior to and during the research, all animals were permanently monitored, with tracking of the body weight of each animal in each group.…”