Neuroprotective role of gallic acid in aflatoxin B₁‐induced behavioral abnormalities in rats

Abstract

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti‐inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1‐induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video‐tracking software demonstrated significant (p < .05) abatement of AFB1‐induced anxiogenic‐like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1‐induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1‐mediated decrease in interleukin‐10 and elevation of inflammatory indices, namely tumor necrosis factor‐α, myeloperoxidase activity, interleukin‐1β, and nitric oxide. Further, GA treatment curtailed caspase‐3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1‐induced neurobehavioral abnormalities by GA involves anti‐inflammatory, antioxidant, and antiapoptotic mechanisms in rats.

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

“…showed that AFB 1 administration induced weight loss in the present study, and this observation is consistent with previous reports (Adedara et al, 2021;Sun et al, 2018).…”

“…increasing the oxidative state of the tissues. Also, the role of RNS in tissue injury has been studied (Adedara et al, 2021;Owumi, Adedara, Akomolafe, et al, 2020;. In this study, we showed that the administration of CA suppressed ROS and RNS generation by reducing the levels of LPO, XO, and RNS in the testis, hypothalamus, and epididymis of male rats treated with AFB 1 .…”

“…AFB 1 is a metabolite whose biotransformation is associated with increased ROS levels with a concurrent decrease in antioxidant defense systems (Kim et al, 2020;Owumi & Dim, 2019;Panth et al, 2016). Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferase (GST) are first-line antioxidant defense systems against ROS production (Adedara et al, 2021;Nowicka-Bauer & Nixon, 2020).…”

“…This toxic intermediate is further detoxified through the glutathione (GSH) conjugation path to AFB 1 ‐ S ‐G conjugate by glutathione S ‐transferase (GST), afterward to AFB 1 ‐mercapturate by N ‐acetyl transferase, and then gets excreted in the urine (Deng et al, 2018; Dohnal et al, 2014). Reduction in tissue levels of GST will drive the conversion of AFB 1 ‐exo‐8,9‐epoxide into genotoxic epoxide, AFB 1 ‐N 7 ‐guanine DNA adult (Guo et al, 2005), preponderant of reactive oxygens and nitrogen species, and inflammatory and apoptotic mediators (Adedara et al, 2021; Owumi, Najophe, et al, 2020). These unstable molecules have a high affinity for cellular macromolecules, for example, nucleic acids, proteins, and phospholipids, causing distinctive hereditary, metabolic, signaling, and cell structural disruptions in animals (Marchese et al, 2018).…”

Biochemical and histological alterations of doxorubicin‐induced neurotoxicity in rats: Protective role of luteolin

“…Moreover, myeloperoxidase (MPO) activity was evaluated according to the previously reported method described by Trush et al, [45,46] using the reaction between O-dianisidine and hydrogen peroxide and absorbance measured spectrophotometrically. MPO catalyzes the oxidation of O-dianisidine, with H 2 O 2 serving as an oxidizing agent, to give a brown-colored oxidized O-dianisidine product, with characteristic absorbance at 460 nm.…”