Abstract
The kidney is a major target organ for the elimination of xenobiotics and is therefore susceptible to tissue injury and impaired excretory function. Acetaminophen (AMP), widely used as an analgesic and antipyretic, is generally safe at therapeutic doses but may cause nephrotoxicity at high doses. Methylene blue (MB), which possesses antioxidant and cytoprotective properties, may help protect against AMP-induced renal injury. This study investigated the protective effects of MB against AMP-induced nephrotoxicity in rats, with particular emphasis on renal histological changes.
Forty-nine rats were randomly divided into seven groups, with seven animals per group, and received the designated treatments over a 13-day experimental period. The control group received distilled water orally, while the MB group received MB at 100 mg/kg body weight. The AMP group received a single oral dose of AMP at 2000 mg/kg on day 7. Two prophylaxis groups received MB orally for seven days before administration of AMP on day 7: the low-dose prophylaxis group received MB 50 mg/kg, whereas the high-dose prophylaxis group received MB 100 mg/kg. Two treatment groups received MB throughout the 13-day period, including after AMP administration: the low-dose treatment group received MB 50 mg/kg, and the high-dose treatment group received MB 100 mg/kg. All animals were sacrificed on day 14, and their kidneys were collected, processed, stained, and examined histologically.
The control animals showed normal renal architecture, including well-preserved glomeruli and renal tubules. In contrast, the AMP group demonstrated clear renal injury, characterized by tubular cellular damage, nuclear condensation and disruption, interstitial edema, and inflammatory-cell infiltration. The MB-only group showed preserved glomerular and tubular architecture with intact capillary beds. Both prophylactic MB groups demonstrated relatively preserved renal structures, although mild mesangial cellularity and tubular epithelial degeneration were observed. The treatment groups showed further preservation of renal architecture. The MB 50 mg/kg treatment group exhibited well-defined glomeruli and capillary beds with organized tubular epithelial lining and protected nuclei. The MB 100 mg/kg treatment group showed properly structured glomeruli, preserved capillary beds, and intact tubular lumina without obvious cellular debris or tissue sloughing.
Overall, MB administration attenuated AMP-induced renal histological damage. Importantly, continued MB administration after AMP exposure produced greater histological preservation than prophylactic administration alone, with an apparent dose-dependent improvement. These findings suggest that MB may have both protective and therapeutic potential against AMP-induced nephrotoxicity.
