The impact of gallic acid on the methotrexate-induced kidney damage in rats

Abstract

Prolonged use of an antineoplastic agent methotrexate (MTX), can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA). Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg) MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE-2) and C-reactive protein (CRP) in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities.

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

“…Although MTX chronotherapy effectively lowered CPR and tumour necrosis factor-α (TNF-α) in rats with collagen induced-arthritis [41] , the highest level of CPR in the present study was in the MTX group. In harmony with our results, CRP and TNF-α were expressed immunohistochemically in the tubular epithelium of MTX-treated rats kidney [13] . According to Famurewa, Folawiyo [12] , the activation of macrophages nuclear factor kappa B(NF-ƙB) seems to play a role in CRP and IL-6 elevation associated with MTX.…”

“…Oxidative stress and lipid peroxidation have been also suggested to play the key role in methotrexate-induced lung injury (MILI) [12] . MTX administration resulted in oxidative-induced damage in kidney [13] , liver [14] and testis [15] . Despite its high significance, the impact of MTX on the lungs has not been frequently reported [11] .…”

Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

“…Thirty-two rats were divided into four groups and each group included 8 rats as illustrated in Table 1. Methotrexate (MTX, Methotrexate 50 mg, TP, Shanxi PUDE Pharmaceutical Co. Ltd., Shanxi, China) was given as described by previous studies as a single dose of 20 mg/kg intraperitoneally (ip) to induce nephrotoxicity [6,20,21]. While, Ginkgo biloba leaf extract (GB, Ginkgo biloba 60, GNC, Pittsburgh, PA, USA, Code 194712) was administered by oral gavage 60 mg/kg/day according to the therapeutic dose documented before in various animal models [22,23,24].…”

Gallic Acid and Gallates in Human Health and Disease: Do Mitochondria Hold the Key to Success?

“…In a mice model of hypoxia/reperfusion cerebral damage, gallic acid increases the viability of the neuronal cells by protecting mitochondria against severe oxidative stress . Oxidative damage–induced nephrotoxicity in murine models has also been found to be ameliorated by gallic acid supplementation . To increase the healing potential of gallic acid, a mitochondria‐targeted gallic acid derivative has been synthesized with greater antioxidative potential.…”