Regular ArticleGender-Related Differences in Susceptibility to Acetaminophen-Induced Protein Arylation and Nephrotoxicity in the CD-1 Mouse
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Assessment of the biochemical pathways for acetaminophen toxicity: Implications for its carcinogenic hazard potential
2021, Regulatory Toxicology and Pharmacology4-methylpyrazole protects against acetaminophen-induced acute kidney injury
2020, Toxicology and Applied PharmacologyCitation Excerpt :Immunohistochemistry studies have also demonstrated positive staining with both anti-APAP and anti-CYP2E1 antibodies in renal proximal tubules (Hart et al., 1995). Cytochrome P450-dependent nephrotoxicity and selective protein covalent binding have been observed in male CD-1 mice (Hoivik et al., 1995) and importantly, both NAPQI formation and activity of CYP2E1 have been shown in human kidney samples, which were significantly higher in males compared to females (Arzuk et al., 2018). Furthermore, histopathological analysis of renal biopsies from APAP overdose patients shows evidence of acute proximal and distal renal tubular necrosis as well as loss of tubular brush border (Björck et al., 1988; Kleinman et al., 1980).
Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats
2020, Life SciencesCitation Excerpt :On the other hand, several other studies have reported that female mice are more resistant to APAP overdose-induced liver damage due to improved detoxification of reactive oxygen metabolites (ROM) with an enhanced recovery of mitochondrial GSH in female mice [15–18]. Furthermore, it was suggested that the observed sex-dependent APAP toxicity was organ-specific, and female rats/mice were less susceptible to hepatotoxicity, but more sensitive to nephrotoxicity [19,20]. As being the dominant sex steroids of females, estrogens were defined to have pro-oxidant or anti-oxidant actions depending on target cells and estrogen receptor (ER) subtypes [21].
Is oxidative stress involved in the sex-dependent response to ochratoxin A renal toxicity?
2018, Food and Chemical ToxicologyCitation Excerpt :However, the influence of sex in OTA-mediated kidney oxidative stress response has not been specifically studied. Indeed, this might be an important aspect to evaluate as sex differences regarding oxidative stress response have been observed in other scenarios such as after giving a high cholesterol diet to Wistar albino rats (Al-Rejaie et al., 2012), acetaminophen to CD-1 mouse (Hoivik et al., 1995) or cisplatin to Swiss albino mice (Naseem et al., 2015). Besides, Lash et al. (1998) found that the rates of S-(1,2,2-trichlorovinyl)glutathione (TCVG) formation in isolated kidney cells from male and female F344 rats were similar, but kidney cytosol and microsomes from males exhibited higher amounts of TCVG formation than the corresponding fractions from females, for both F344 rats and B6C3F1 mice.
Mechanisms of Toxicant-Induced Acute Kidney Injury
2018, Comprehensive Toxicology: Third EditionGender-specific expression of ATP-binding cassette (Abc) transporters and cytoprotective genes in mouse choroid plexus
2017, ToxicologyCitation Excerpt :CYP2E1 is involved in the bioactiviation of APAP in the kidney. Previous studies have shown that higher renal CYP2E1 expression in male kidney contributes to greater susceptibility to APAP induced renal toxicity compared to female mice (Hoivik et al., 1995; Mazer and Perrone, 2008). Our data on the CP gender differences may provide a further step toward better understanding the impact of drugs and other organic metabolites on the brain.