Unraveling the combined deleterious effects of ochratoxin A and atrazine upon broiler's health: Toxicopathological, serum biochemical and immunological perspectives.

Atrazine, a herbicide, is used for eradication of broad-leaved herbs in corn crop; and ochratoxins, particularly ochratoxin A (OTA), are major pollutants of poultry diet. Existence of both of these hazardous chemicals as residues is obvious as elucidated by various epidemiological findings. The present study was designed to investigate toxicopathological, serum biochemical and immunological alterations incurred by atrazine alone and/or, in combination with OTA in broilers. For this purpose, one-day old broiler chicks (n = 180) were purchased from a local hatching unit and were fed two levels of atrazine (50 and 150 mg/kg) and one level of OTA (100 µg/kg) in different combinations. Results of this experiment showed a significant reduction in feed intake, body weight gain, relative organ weights, serum total protein, albumin and globulin while there was a significant increase in urea and creatinine levels, decreased antibody response to sheep red blood cells, reduced lymphoproliferative response and phagocytic capacity in groups given OTA and atrazine individually in feed and these effects became more pronounced when atrazine was given in combination with OTA suggesting synergistic effects of both toxicants for each other.

Pachypodol attenuates Perfluorooctane sulphonate-induced testicular damage by reducing oxidative stress.

Perfluorooctane sulfonate (PFOS) is an endocrine disruptor chemical (EDC) with potentially adverse effects on the male reproductive system. Pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxyflavone) is a promising flavonoid isolated from Pogostemon cablin (Blanco) Benth that shows a broad range of pharmacological properties. However, the potential curative effects of pachypodol on testicular toxicity are not available until now. Therefore, this research was proposed to examine the efficiency of pachypodol against PFOS-induced testicular toxicity in adult male rats. The experiments were conducted on Sprague-Dawley rats (n = 48), which were equally distributed into four groups: control, PFOS (20 mg/kg), PFOS + Pachypodol (20 mg/kg + 10 mg/kg respectively), and Pachypodol (10 mg/kg). After 56 days of treatment, testes were excised by slaughtering rats, weighed, and stored till further analysis. The estimated parameters include biochemical markers, spermatogenic indices, hormonal and histopathological profiles. PFOS exposure disturbed the biochemical profile by altering the antioxidant/oxidant balance. For instance, it decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while increasing the concentration of reactive oxygen species (ROS) and level of thiobarbituric acid reactive substances (TBARS). PFOS intoxication also led to a notable decline in viability, motility, epididymal sperm count, and the number of HOS coiled-tail sperms, whereas the higher level of abnormality in the head, mid-piece, and tail of sperms were observed. Besides, it lowered luteinizing hormone (LH), follicle-stimulating hormone (FSH), and plasma testosterone. In addition, PFOS exposure led to histopathological damages in testicles. However, pachypodol treatment potently alleviated all the illustrated impairments in testes. Conclusively, our results demonstrate the promising free-radical scavenging activity of pachypodol, a novel phytochemical, against the PFOS-instigated testicular dysfunctions.

Protective effects of vitexin on cadmium-induced renal toxicity in rats.

Cadmium (Cd) is an industrial contaminant that poses severe threats to human and animal health. Vitexin (VIT) is a polyphenolic flavonoid of characteristic pharmacological properties. We explored the curative role of vitexin on Cd-induced mitochondrial-dysfunction in rat renal tissues. Twenty-four rats were equally divided into four groups and designated as control, Cd, Cd + vitexin and vitexin treated groups. The results showed that Cd exposure increased urea and creatinine levels while decreased creatinine clearance. Cd reduced the activities of antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in the Cd exposed group. Cd exposure significantly (p < 0.05) elevated the reactive oxygen species (ROS) and Thiobarbituric acid reactive substances (TBARS) levels in rat kidney. Cd also caused a significant (p < 0.05) reduction in the mitochondrial TCA-cycle enzymes, including isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, and malate-dehydrogenase activities. Besides, mitochondrial respiratory chain enzymes, including NADH-dehydrogenase, coenzyme Q-cytochrome reductase, succinic-coenzyme Q, and cytochrome c-oxidase activities were also decreased under Cd exposure. Cd exposure also damaged the mitochondrial membrane potential (MMP). However, VIT treatment potentially reduced the detrimental effects of Cd in the kidney of rats. In conclusion, our study indicated that the VIT could attenuate the Cd-induced renal toxicity in rats.

Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration.

Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized calcium-binding adapter molecule-1 (Iba-1), cyclooxygenase-2 (COX-2), tumor necrotic factor-α (TNF-α), toll-like receptors (TLR4), and nuclear factor-κB (NF-κB) by down-regulating p-JNK as evidenced by immunohistochemical results. Moreover, treatment with A3 reduced the infarction area and neurobehavioral deficits. We employed ATRA to antagonize Nrf2, which abrogated the neuroprotective effects of A3 to further assess the possible involvement of the Nrf2 pathway, as demonstrated by increased infarction and hyperexpression of inflammatory markers. Together, our findings suggested that A3 could activate Nrf2, which in turn regulates the downstream antioxidants, eventually mitigating MCAO-induced neuroinflammation and neurodegeneration.