Anti-inflammatory and Anti-oxidative effects of Atorvastatin and Roflumilast against Methotrexate induced hepatotoxicity in Rats

Abstract

Background: Methotrexate (MTX) is an antagonist of folic acid, frequently recommended as a cytotoxic medication to treat a number of illnesses, including leukemia and inflammatory diseases like rheumatoid arthritis and psoriasis. However, because of its severe adverse effects, particularly hepatotoxicity, its usage in clinical practice has been restricted. Members of the Statins category, sometimes referred to as HMG-CoA reductase inhibitors, include atorvastatin (ATR), which is frequently used to treat excessive cholesterol and lower the risk of cardiovascular illnesses. Roflumilast (ROF), a phosophdiestrase 4 inhibitor, assuming in   treatment the chronic obstructive lung disease and has been revealed to be necessary antioxidant and anti-inflammatory properties. The current study investigated the potential hepatoprotective benefits associated with ATR and ROF in preventing MTX-induced damage to the liver in rats. Methods: 24 Wistar rats (male) were separated to four groups. Acute liver injury was induced by a dose of 20 mg/kg MTX intraperitoneally (ip.) administration for seven consecutive days . Control group: The usual intravenous saline injections were given daily. Induction group: daily IP injection of MTX (20 mg/kg). Third group (ATR+MTX) once daily (15 mg/kg, oral + 20 mg/kg, IP. Fourth (ROF+MTX) group ; Every day (5 mg/kg, oral plus 20 mg/kg; i.p) was administered to  ten days. Treatment groups (third and fourth) began three days with ATR and ROF, orally before  MTX injection, and continued for ten days consecutively. Results: When MTX (20 mg/kg, IP) was administered for 7 days consecutively, the levels of hepatic antioxidant enzymes, for instance glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT], were significant reduced. However , the levels of malondialdehyde [MDA] and inflammatory markers; Interleukins (IL-6 and IL-1), tumor necrosis factor-alpha [TNF-a], and the liver enzymes significantly rose; alanine aminotransferase [ALT] and aspartate aminotransferase [AST]. The changes in these measures were considerably reduced after ten days of ATR and ROF treatment. In conclusion, the results suggest that ATR and ROF may be useful therapeutic agents for reducing the effects of MTX-induced liver damage in rats. It look like from our outcomes that the treatment groups appear to alleviate MTX-induced liver damage by moderating inflammation and oxidative stress in the liver.