Isorhamnetin is a hepatoprotective flavonoid molecule derived from the leaves and fruits of Hippophae rhamnoides L. However, the protective effect of isorhamnetin on acetaminophen (APAP) induced hepatotoxicity is still unknown. Thus, we aimed to investigate the lipid-lowering, anti-inflammatory, and hepatoprotective effects of isorhamnetin on APAP-induced hepatotoxicity in mice. Hepatotoxicity was induced by a single injection of APAP (300 mg/kg, intraperitoneally). Isorhamnetin (50 or 100 mg/kg, orally) and N-acetylcysteine (NAC) (200 mg/kg, orally), or vehicle control, were administered 1 h before the administration of APAP. Total antioxidant status (TAS) and total oxidative status (TOS) of liver tissue and levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were analyzed by ELISA. Lipid profiles and liver function parameters were measured using an autoanalyzer. In addition, liver tissue was examined histopathologically. Isorhamnetin treatment significantly reduced the APAP-induced increase in the liver weight and liver index; it also reduced the APAP-induced increase in serum liver parameters (ALT, AST, ALP, and LDH) (p < 0.05). Isorhamnetin significantly reduced APAP-induced oxidative stress and inflammation by increasing TAS levels and decreasing TOS, TNF-α, IL-1β, and IL-6 levels (p < 0.05). Moreover, isorhamnetin treatment significantly regulated lipid profiles (TG, T-C, LDL-C, and HDL-C levels) that changed in response to APAP administration (p < 0.05). In histopathological examination, liver degeneration observed in the APAP group was significantly reduced in the NAC and isorhamnetin-treated groups (p < 0.05). This study suggests that isorhamnetin has a significant protective effect on APAP-induced hepatotoxicity in mice through its lipid-lowering, antioxidant, and anti-inflammatory effects.

This study was designed to investigate the possible antioxidant, antiapoptotic and neuroprotective effects of nobiletin on cisplatin-induced neurotoxicity rat model by evaluating neurotrophins, ant...

Aflatoxins (AFs) are metabolised in two main phases in the liver. Cytochrome p450 enzyme (CYP) 1A1 and CYP2A6 are expressed through AhR, CAR and PXR nuclear receptors in phase-1 biotransformation of AFs. This study is the first to examine phase-1 biotransformation mechanisms of AF and the activity of Nigella sativa seed (NS) and its active ingredient thymoquinone (TQ) on these enzymes and receptors at the molecular level in broilers. Six groups of one day old broiler chicken (20 animals per group) were fed either control feed or a diet containing Aspergillus parasiticus NRRL 2999 culture material (total AFs 2 mg/kg), TQ (300 mg/kg), and NS (5%), either alone or as AF + TQ and AF + NS. Randomly selected from each group, 10 chicks were necropsied, and the livers were removed. Histopathological examination and serum biochemistry results revealed that AF caused hydropic and fatty degenerations, periportal inflammatory infiltrations, acinar arrangement, and biliary duct proliferation in livers and a significant increase at AST, ALT, ALP and GGT levels while significant decreases at serum cholesterol and total protein levels. These aflatoxicosis lesions and deteriorations in biochemistry levels were significantly ameliorated by NS or TQ (p < 0.05). AF was immunohistochemically found to increase strongly the nuclear receptors of AhR, PXR, CAR, and the enzyme activity of CYP1A1 and CYP2A6 responsible for its metabolism, leading to the emergence of toxic effects. Addition of TQ or NS to AF-containing diets improved the negative effects of AF on these receptors and enzymes significantly (p < 0.05). It was concluded that TQ and NS successfully alleviated liver injury by inhibiting or reducing the bioactivation of AF through phase-1 nuclear receptors and CYP-450 enzymes modulation.

1. Aflatoxins (AFs) are metabolites which especially have toxic effects on proteins, and are detoxified by the aflatoxin-B₁ aldehyde reductase (AFAR) pathway. In this pathway, the aldo-keto reductase family 7, member A2 (AKR7A2) enzyme, which is controlled by nucleic-related erythroid factor 2 (Nrf2), plays an active role. However, data on the efficacy of this critical pathway in broilers is limited. 2. The aim of the following study was to investigate the changes in the expression levels of AKR7A2, Nrf2, and caspase-3, and the effects of Nigella sativa seeds (NS), thymoquinone (TMQ), and bentonite (BNT) in broilers exposed to AFs. 3. One-hundred broilers were divided into ten groups (control (CNT); AF; NS; TMQ; BNT; AF+TMQ; AF+NS; AF+BNT; AF+BNT+NS; AF+BNT+TMQ) and fed for 28 d. AF, TMQ, NS and BNT were added to diets at levels of 2 mg/kg, 300 mg/kg, 50 g/kg and 10 g/kg respectively. 4. The addition of AF to the diet decreased AKR7A2 and Nrf2 levels dramatically, but increased caspase-3 (P < 0.01). TMQ, NS and BNT additions to the diet eliminated all negative effects caused by AF (P < 0.01); and AKR7A2 and Nrf2 were further raised in TMQ and NS groups when compared to the control group. TMQ and NS showed a positive effect on detoxification parameters when given together with BNT. 5. Supplementation with NS and TMQ enhanced AF detoxification via the AFAR pathway, by increasing AKR7A2 and Nrf2 levels, in addition to reducing hepatocyte apoptosis.

Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin‐induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL‐18, KIM‐1, and NGAL levels, whereas ALA treatment significantly reduced KIM‐1 levels compared to the gentamicin‐only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF‐2, CAS‐3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF‐B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin‐induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.