Protective Effects of Lactobacillus rhamnosus GG Against Methotrexate-Induced Oxidative Renal Toxicity

Methotrexate (MTX) is commonly prescribed for various malignant and autoimmune conditions, but it can cause significant oxidative and functional impairment in renal tissue. Lactobacillus rhamnosus GG. (LGG) is a well-known probiotic with biological activities that support antioxidant balance. This study investigated the impact of LGG on MTX-induced kidney damage. Male Sprague-Dawley rats were divided into four groups: physiological saline-treated control group; a group receiving MTX alone; a group receiving MTX alongside a low dose of LGG; and a group receiving MTX alongside a high dose of LGG. MTX was administered as single dose (20 mg/kg/bw) intraperitoneally and LGG (low dose 1 x 10⁹ CFU/day and high dose 5 × 10⁹ CFU/day, respectively) orally for five days. On day six, blood and kidney samples were collected and examined for oxidative indicators, enzymatic antioxidant responses, and renal functional markers. MTX significantly increased in glomerular filtration markers in serum and elevated key indicators of oxidative stress in renal tissues. More so, MTX demonstrated to disrupt renal ionic homeostasis, such as declined sodium/potassium-ATPase, paraoxonase, and increased lactate dehydrogenase, carbonic anhydrase, xanthine oxidase, myeloperoxidase, and arginase activities. In contrast, LGG supplementation has been shown to effectively reverse all MTX-induced biochemical alterations in both serum and renal tissue. We can suggest that LGG can provide significant protection against oxidative renal toxicity induced by MTX in rats.