Underlying biochemical effects of intermittent fasting, exercise and honey on streptozotocin-induced liver damage in rats.

Purpose: Derangements of liver transcriptional factors and enzymes have important implications in diabetes-induced related complications. Hence, this study which consists of two experimental phases was aimed at evaluating the possible underlying molecular mechanisms of intermittent fasting (IF), exercise starvation and honey in streptozotocin (STZ)-mediated liver damage in diabetic rats. Methods: The diabetic rats were treated orally with distilled water (0.5 ml/kg), IF, starvation and honey at 1 g/kg body weight in the non-diabetic phase for four (4) weeks. After STZ injections, four (4) weeks of IF, exercise, starvation, and honey therapy were used as interventions prior to a biochemical evaluation of the liver. Results: IF and exercise greatly decreased liver transcription factor (resistin, SREBP-1c), inflammatory cytokines/enzyme (TNF-α, IL-6, IL-1ß, MPO) as well as oxidative and nitrergic stress with correspondence increased liver PPAR-γ, IL-10, SOD, CAT and GSH in diabetic rats unlike starvation and honey regimen relative to diabetic controls. Furthermore, IF and exercise significantly improved hepatic glycogen synthase and decreased glycogen phosphorylase in diabetic rats compared to the diabetic control group, but starvation and honey therapy had no such influence. IF and exercise strategically reduces STZ-induced liver metabolic disorder via through modulation of liver transcriptional factors and inhibition of pro-inflammatory cytokines, oxido-nitrergic and adipokine signaling pathway.

Kolaviron, a flavonoid-rich extract ameliorates busulfan-induced chemo-brain and testicular damage in male rats through inhibition of oxidative stress, inflammatory, and apoptotic pathways.

Previous reports revealed that increased oxidative stress with up-regulated inflammatory proteins and apoptotic factors have serious implications in busulfan-induced chemo-brain and testicular damages. Hence, we investigated the potential reversal effects of kolaviron (KV), a neuro-active extract rich in flavonoids with proven anti-oxido-inflammatory and anti-apoptotic properties, on busulfan-induced oxidative damage, inflammatory proteins, and apoptosis in the brains and testes of male rats. In the treatment-regimen, animals in groups 1 and 2 had saline (10 ml/kg/p.o./day) and dimethyl sulfoxide (DMSO; 10 ml/kg/p.o./day), group 3 received KV extract (200 mg/kg/p.o./day), group 4 was given busulfan (50 mg/kg/p.o./day) and animals in group 5 were pretreated with busulfan (50 mg/kg/p.o./day) successively for 56 days in addition to KV extract (200 mg/kg/p.o./day) from days 29-56. Non-spatial memory function was valuated with a novel-object recognition memory test. Thereafter, testicular and brain oxidative/antioxidant status, proinflammatory- and apoptotic-related proteins, testicular enzymatic markers were evaluated respectively. Kolaviron extract improved cognitive function by increasing exploration of novel-object of busulfan-treated rats. Kolaviron extract reversed busulfan-mediated increased malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and decreased superoxide dismutase, catalase, glutathione, and glutathione-peroxidase in brains and testes as well as the testicular enzyme markers. Increased brain and testicular weights, and TNF-α, IL-1ß, and NF-κß productions due to busulfan administration were also reduced by the extract. The reduced testicular B-cell lymphoma-2, sperm mitochondrial cytochrome-C, and membrane potential, increased DNA fragmentation, caspases -3 and -9 levels were also profoundly reversed by KV. Additionally, KV extract ameliorated busulfan-induced testicular histopathological changes in rats. Conclusively, KV extract reverses busulfan-induced neuroendopathobiological derangements via oxidative stress inhibition, down-regulation of inflammatory and apoptotic mediators in rats' brains and testes. PRACTICAL APPLICATIONS: Busulfan is an orally effective chemotherapy drug widely used for cancer treatment. It has been reported that chronic usage of busulfan increases the tendency for carcinogenic and teratogenic activities with severe side effects on the functions of the gonads and other body organs such as brain, popularly regarded as chemo-brain. When taken over a prolonged period of time, busulfan causes sterility in animals and destroyed spermatogonial stem cells along with the seminiferous tubules and sperm morphology of animals as well as memory impairments. The findings from the study revealed that KV extract prevent busulfan-induced cognitive and testicular impairments following kolaviron supplementation. Thus, the findings from this scientific investigation suggest that KV extract could improve the quality of reproductive life and cognitive functions of male patients during busulfan chemotherapy, particularly during prolonged therapy.

Duration-dependent effects of high dose of phthalate exposure on semen quality in adult male rats.

OBJECTIVE: To determine the length of exposure to high doses of phthalate that might affect sperm quality in adult male Wistar rats. METHODS: Forty-two (42) adult male Wistar rats (weighing 150-200 g) were randomly assigned into six groups (n=7): Group A received 0.5 mL of distilled water - placebo - and served as controls; groups B, C, D, E and F received Phthalate (750 mg/kgbw) for 1, 3, 5, 7 and 9 weeks, respectively. The data obtained from the study was expressed as Mean ± SEM with a p-value <0.05 considered significant. The data was analyzed with one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test using GraphPad Prism, version 8. RESULTS: The results showed a statistically significant (p<0.05) decrease in testicular weight in the rats exposed to 750 mg/kg of phthalate for 3, 5, 7 and 9 weeks when compared with the controls. Sperm count, motility and viability were also significantly (p<0.05) reduced, while sperm cells with abnormal morphology had increased counts in the groups exposed for 3, 5, 7 and 9 weeks when compared with controls. Serum zinc and magnesium were also significantly reduced (p<0.05) in the subjects treated for 1, 3, 5, 7 and 9 weeks when compared with controls. CONCLUSIONS: The dosage of phthalate adopted in this study was deleterious to testicular function when rats were exposed to it for as short a period as three weeks.