Luteolin treatment attenuates cypermethrin-induced oxidative stress, neurobehavioural, genetic and histopathological alterations and limits gut-blood bacterial translocation in rats

Cypermethrin (Cyp) is a potent synthetic pyrethroid insecticide which is effective against numerous pests in agriculture, public health, and animal husbandry. This study was designed to investigate the protective effects of luteolin (Lut) against Cyp-induced toxicity affecting the bone marrow, gastrointestinal tract and brain in Wistar rats. Forty (40) male Wistar rats were divided equally into four groups ( n = 10 per group), including control, Cyp (25 mg/kg for 28 days), Cyp + Lut (25 mg/kg + 50 mg/kg co-treatment for 28 days) and Lut (50 mg/kg for 28 days) groups. On the 27th and 28th days, the rats were subjected to neurobehavioural tests. Freshly voided faeces and spleen were collected for enumeration of Escherichia coli. The femur bone marrow tissues were harvested for micronucleus assay, while the brain, stomach and colon were processed for biochemical assays and histopathological examination. Luteolin treatment significantly improved the hanging latency of rats on a hanging wire. It also increased the frequencies of grid crossing and rearing, but reduced the freezing time, center square duration and amount of faecal boli in open field test. Moreover, Lut reduced the frequency of micro-nucleated polychromatic erythrocytes (MnPCEs/1000 PCEs) in the bone marrow and mitigated Cyp-induced histopathological alterations including neuronal atrophy and gliosis in the cerebral cortex and cerebellum, as well as hyperplasia of colonic glandular epithelium and degenerative and necrotic lesions of the ileal and colonic mucosa. Furthermore, Lut effectively limited tissue oxidative stress by reducing the levels of oxidants (malondialdehyde, MDA; hydrogen peroxide, H 2 O 2 ; nitric oxide, NO and advanced oxidation protein products, AOPP) and improving the antioxidants (reduced glutathione, GSH; thiol groups; glutathione S-transferase, GST and glutathione peroxidase, GPx). Remarkably, Escherichia coli counts in the faeces and spleen showed marked reduction in bacterial translocation from gut to the blood in Lut-treated rats. To sum up, the results from this study showed that Lut is an effective counteracting agent against Cyp-induced tissue damage and is recommended for prevention of intestinal, brain and bone marrow toxicities induced by Cyp exposure.