Caffeic acid mitigates aflatoxin B1-mediated toxicity in the male rat reproductive system by modulating inflammatory and apoptotic responses, testicular function, and the redox-regulatory systems

J Food Biochem. 2022 May;46(5):e14090. doi: 10.1111/jfbc.14090. Epub 2022 Feb 2.

Abstract

Aflatoxin B1 (AFB1 ) is a toxic metabolite of public health concern. The present study investigates the protective effects of caffeic acid (CA) against AFB1 -induced oxidative stress, inflammation, and apoptosis in the hypothalamus, epididymis, and testis of male rats. Five experimental rat cohorts (n = 6) were treated per os for 28 consecutive days as follows: Control (Corn oil 2 ml/kg body weight), AFB1 alone (50μg/kg), CA alone (40 mg/kg) and the co-treated rat cohorts (AFB1 : 50μg/kg + CA1: 20 or 40 mg/kg). Following sacrifice, the biomarkers of hypothalamic, epididymal, and testicular toxicities, antioxidant enzyme activities, myeloperoxidase (MPO) activity, as well as levels of nitric oxide (NO), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were analysed spectrophotometrically. Besides, the concentration of tumour necrosis factor-alpha (TNF-α), Bcl-2 and Bax proteins were assessed using ELISA. Results showed that the AFB1 -induced decrease in biomarkers of testicular, epididymal and hypothalamic toxicity was significantly (p < .05) alleviated in rats coexposed to CA. Moreover, the reduction of antioxidant status and the increase in RONS and LPO were lessened (p < .05) in rats co-treated with CA. AFB1 mediated increase in TNF-α, Bax, NO and MPO activity were reduced (p< .05) in the hypothalamus, epididymis, and testis of rats coexposed to CA. In addition, Bcl-2 levels were reduced in rats treated with CA dose-dependently. Light microscopic examination showed that histopathological lesions severity induced by AFB1 were alleviated in rats coexposed to CA. Taken together, the amelioration of AFB1 -induced neuronal and reproductive toxicities by CA involves anti-inflammatory, antioxidant, antiapoptotic mechanisms in rats. PRACTICAL APPLICATIONS: The beneficial antioxidant effects of caffeic acid (CA) are attributed to CA delocalized aromatic rings and free electrons, easily donated to stabilize reactive oxygen species. We report in vivo findings on CA and AfB1 mediated oxidative stress and reproductive dysfunction in rats. CA conjugated esters including chlorogenic acids are widely distributed in plants, and they act as a dietary source of natural defense against infections. CA can chelate heavy metals and reduce production of damaging free radicals to cellular macromolecules. Along these lines, CA can stabilize aflatoxin B1-epoxide as well and avert deleterious conjugates from forming with deoxyribonucleic acids. Hence CA, as a dietary phytochemical can protect against the damaging effects of toxins including aflatoxin B1 that contaminate food. CA dose-dependently abated oxidative, inflammatory, and apoptotic stimuli, improved functional characteristics of spermatozoa and reproductive hormone levels, and prevented histological alterations in experimental rats' hypothalamus and reproductive organs brought about by AFB1 toxicity.

Keywords: aflatoxin B1; apoptosis; caffeic acid; oxido-inflammation; reproductive toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1* / metabolism
  • Aflatoxin B1* / toxicity
  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Biomarkers / metabolism
  • Caffeic Acids / pharmacology
  • Male
  • Oxidation-Reduction
  • Rats
  • Testis
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Caffeic Acids
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Aflatoxin B1