Effects of Lactobacillus rhamnosus GG. against methotrexate-induced kidney injury

Methotrexate (MTX) is a widely utilized chemotherapeutic agent in the treatment of various autoimmune diseases and malignancies. However, its prolonged utilization can result in tissue damage due to oxidative stress in multiple organs, primarily the kidneys. Lactobacillus rhamnosus GG. (LGG) is a probiotic microorganism that has been shown to possess antioxidant and anti-inflammatory properties. The present study was conducted with the objective of investigating the potential protective effects of LGG against oxidative damage to the rat kidney tissues induced by MTX. The current, study comprised 32 male Sprague-Dawley rats, which were divided into four groups of random selection: a control group; an experimental group receiving a single intraperitoneal dose of 20 mg/kg MTX; an MTX+LGG1 group receiving an oral dose of 1×10⁹ CFU/day for five days; and an MTX+LGG5 group receiving an oral dose of 5×10⁹ CFU/day for five days. On the sixth day, the fasted rats were euthanized under anesthesia. Blood and kidney tissue samples were collected from the rats. Tissue samples were analyzed for oxidative stress, antioxidant defense, ion balance, and kidney function parameters. MTX administration significantly increased serum urea, uric acid, and creatinine levels, renal lipid peroxidation, reactive oxygen species, advanced oxidized protein products, nitric oxide, and hydroxyproline levels, while decreasing glutathione levels. The antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and Na+/K+-ATPase, and paraoxonase activities decreased significantly, while lactate dehydrogenase, carbonic anhydrase, xanthine oxidase, myeloperoxidase, and arginase activities increased. These effects were reversed when low and high doses of LGG were administered to the MTX group. The findings suggest that LGG may be an effective bioprotective agent against MTX-induced oxidative kidney damage, and that this effect is likely related to the restoration of redox balance and the preservation of membrane integrity.