Aspergillus awamori attenuates ochratoxin A-induced renal and cardiac injuries in rabbits by activating the Nrf2/HO-1 signaling pathway and downregulating IL1β, TNFα, and iNOS gene expressions

Abstract

Ochratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study explored the protective effect of different concentrations of Aspergillus awamori (A. awamori) against OTA (0.3 mg/kg diet) induced renal and cardiac damage by exploring its mechanism of action in 60 New Zealand white male rabbits. Dietary supplementation of A. awamori at the selected doses of 50, 100, and 150 mg/kg diet, respectively, for 2 months significantly improved the rabbit’s growth performance; modulated the suppressed immune response and restored the altered hematological parameters; reduced the elevated levels of renal injury biomarkers such as urea, creatinine, and alkaline phosphatase; and increased serum total proteins concentrations. Moreover, it also declined enzymatic activities of cardiac injury biomarkers, including AST, LDH, and CK-MB. A. awamori alleviated OTA-induced degenerative and necrotic changes in the kidney and heart of rabbits. Interestingly, A. awamori upregulated Nrf2/OH-1 signaling pathway. Therefore enhanced TAC, CAT, and SOD enzyme activities and reduced OTA-induced oxidative and nitrosative stress by declining iNOS gene expression and consequently lowered MDA and NO levels. In addition to attenuating renal and cardiac inflammation via reducing IL-1β, TNF-α gene expressions in a dose-dependent response. In conclusion,this is the first report to pinpoint that dietary incorporation of A. awamori counteracted OTA-induced renal and cardiac damage by potentiating the rabbit’s antioxidant defense system through its potent antioxidant, free radical scavenging, and anti-inflammatory properties in a dose-dependent response. Based on our observations, A. awamori could be utilized as a natural protective agent against ochratoxicosis in rabbits. Graphical abstract

Evaluation of the Expression of RCC and KIM-1 Biomarkers in Nephrotoxicity of Rabbits Treated with Ochratoxins A

“…[18,20]. These findings were in agreement with [21], while [22] reported that rabbits given OTA demonstrated a variety of histological changes, hyperemia in glomerular capillaries, interstitial vasculature, and clearly visible vacuolar tubular epithelial degradation. Other renal tubules also showed cystic dilatation with pressure atrophy on neighboring tubules.…”

Simultaneous Occurrence of Mycotoxins Citrinin and Ochratoxin A in Popcorn Grains and Their Biological Effect on some Physiological Blood Parameters

“…The increase in (MCH) analysis is attributed to liver disease or cancer, while the decrease from the control treatment indicates anemia [15]. These results were similar to the findings of Assar et al (2022) [16] , which showed anemia as a decrease in the numbers of red blood cells and lymphopenia, and differed in an increase in WBC, MCV and MON, Results for MCH and MCHC did not agree with OTA treatment , while they were identical to CIT treatment When New Zealand rabbits were treated with a dose of 0. [18] demonstrated elevated MCV and MCH while white blood cell (WBC), hemoglobin (HB), red blood cell (RBC), Haematocrit (PCV) and MCHC) were observed to be significantly decreased in Liza ramada fish fed OTA at a dose of Its concentration is 1 mg/kg.…”

Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations

“…It is commonly believed that the molecular imbalance of oxidative stress contributes to the progression and development of acute and chronic kidney diseases [19][20][21]. Administration of CP could promote a significant (p < 0.05) increase in MDA levels and a significant (p < 0.05) decrease in the antioxidant capacity as revealed by a decline in the renal…”