Caffeic acid mitigates aflatoxinB1‐mediated toxicity in the male rat reproductive system by modulating inflammatory and apoptotic responses, testicular function, and the redox‐regulatory systems

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.

The Hydrophobic Extract of Sorghum bicolor (L. Moench) Enriched in Apigenin-Protected Rats against Aflatoxin B1-Associated Hepatorenal Derangement

“…Exposure of animals and humans to AFB 1 continues to be of severe concern in semi-arid tropical regions of Asia and Africa. Accidental ingestion of AFB 1 through contaminated food products can cause toxicity to organs such as the liver, kidney, hypothalamus, testis, epididymis, and heart [ 21 , 22 , 24 , 27 ]. The concomitant effects of AFB 1 -induced toxicities include growth retardation, malnutrition, and immune suppression [ 15 , 16 ].…”

“…The mechanisms of AFBO toxicity are known to be through the formation of protein adducts, DNA adducts, and lipid peroxidation. Uncontrolled degradation of functional biological molecules following unfettered exposure to AFB 1 has been observed to deplete the redox buffering system of rats, thereby predisposing cells to oxidative stress, inflammation, and programmed cell death [ 20 , 21 , 22 ]. Nonetheless, there is a safe pathway for removing AFBO from the enterocytes and hepatocytes via the second phase of biotransformation mediated by glutathione S-transferase (GST).…”

“…Previous studies reported the harmful effects of AFB 1 on the reproductive system [ 21 ], the endocrine system [ 25 ], the central nervous system [ 26 ], the cardiovascular system [ 27 ], and the immune system [ 28 ]. These reports reiterate that direct exposure to AFB 1 could promote the development of disease and infection in animals and humans, hence the need to mitigate indiscriminate exposure to AFB 1 and its associated health sequela.…”

May phytophenolics alleviate aflatoxins-induced health challenges? A holistic insight on current landscape and future prospects

“…Caffeic acid in the concentration of 40 mg/kg exhibited protective effects in reproduction system of male rats exposed to 50 μg/kg/b.w. AFB1 through modulation of antioxidant enzymes, apoptosis, and inflammatory factors ( 425 ). Apigeninidin-rich extracts of Sorghum bicolor L. Moench (ASBEs) including ASBE-05/06/07 modulated inflammation and apoptosis mechanisms in kidney and liver of rats exposed to 50 μg/kg doses of AFB1 ( 426 ).…”

Apigeninidin-enriched Sorghum bicolor (L. Moench) extracts alleviate Aflatoxin B1-induced dysregulation of male rat hypothalamic-reproductive axis

“…4 Owumi et al reported disruption of serum hormone levels in AFB 1 -treated rats, and it caused prolactinemia while reducing follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. 2,13,14 In addition, AFB 1 reduces the activity of antioxidant enzymes and levels of endogenous antioxidants, elevates inflammation biomarkers, and induces pathological lesions in rats’ testicular and epididymal tissues, 15 ultimately rendering male animals infertile.…”