Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.

Despite the effectiveness of doxorubicin (DOX) in the management of a wide range of cancers, a major challenge is its cardio-toxic effect. Oxidative stress, inflammation, and apoptosis are major pathways for the cardiotoxic effect of DOX. On the other hand, acetate reportedly exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. This particular research assessed the impact of acetate on cardiotoxicity induced by DOX. Mechanistically, acetate dramatically inhibited DOX-induced upregulation of xanthine oxidase and uric acid pathway as well as downregulation of Nrf2/HO-1 signaling and its upstream proteins (reduced glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione, and catalase, glutathione reductase). In addition, acetate markedly attenuated DOX-driven rise inTNF-α, NFkB IL-6 and IL-1ß expression, and myeloperoxidase activity. Furthermore, acetate significantly ameliorated DOX-led suppression of Bcl-2 and Ca2+-ATPase activity and upregulation of Bax, caspase 3, and caspase 9 actions. Improved body weight, heart structural integrity, and cardiac function as depicted by cardiac injury markers convoyed these cascades of events. Summarily, the present study demonstrated that acetate protects against DOX-induced cardiotoxicity by upregulating Nrf2/HO-1 signaling and downregulating NFkB-mediated activation of Bax/Bcl-2 and caspase signaling.

Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats.

AIM: This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. MATERIALS AND METHODS: Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. RESULTS: Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1ß), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3ß-HSD/17ß-HSD. CONCLUSION: This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.

Buchholzia coriacea seed induce antifertility by interfering with steroidogenic enzymes and inflammatory cytokines in rat testis.

Buchholzia coriacea has been reported to possess antifertility activities but little is known of the mechanisms responsible. This study was therefore designed to examine the mechanism responsible for the action of Buchholzia coriacea. Eighteen male Wistar rats (180-200 g) were used for this study. They were grouped into 3 (n = 6) namely, Control, Methanolic fraction of Buchholzia coriacea (MFBC) 50 mg/kg, and MFBC 100 mg/kg administered orally with respective dosage. After 6 weeks of administration, rats were euthanized, serum collected, while testes, epididymis and prostate were excised and homogenized. Testicular protein and testosterone, aromatase and 5α-reductase enzyme, 3ß hydroxysteroid dehydrogenase (HSD), 17ß-HSD, interleukin (IL) 1ß, IL-10 and Prostatic specific enzyme antigen (PSA) were assessed and data analyzed with ANOVA. There were significant increases in 3ß-HSD and 17ß-HSD levels in the MFBC 50 mg/kg with corresponding decreases in MFBC 100 mg/kg when compared to control. IL-1 was decreased in both doses while IL-10 increased in both doses compared to control. 5-α reductase enzyme was significantly decreased in the MFBC 100 mg/kg relative to the control. Testicular protein, testosterone and aromatase enzyme were not significantly different at both doses compared to control. PSA was significantly increased in the MFBC 100 mg/kg but not the 50 mg/kg relative to control. MFBC exhibits antifertility properties by interfering with testicular enzymes and inflammatory cytokines.

Significance of African Diets in Biotherapeutic Modulation of the Gut Microbiome.

Diet plays an essential role in human development and growth, contributing to health and well-being. The socio-economic values, cultural perspectives, and dietary formulation in sub-Saharan Africa can influence gut health and disease prevention. The vast microbial ecosystems in the human gut frequently interrelate to maintain a healthy, well-coordinated cellular and humoral immune signalling to prevent metabolic dysfunction, pathogen dominance, and induction of systemic diseases. The diverse indigenous diets could differentially act as biotherapeutics to modulate microbial abundance and population characteristics. Such modulation could prevent stunted growth, malnutrition, induction of bowel diseases, attenuated immune responses, and mortality, particularly among infants. Understanding the associations between specific indigenous African diets and the predictability of the dynamics of gut bacteria genera promises potential biotherapeutics towards improving the prevention, control, and treatment of microbiome-associated diseases such as cancer, inflammatory bowel disease, obesity, type 2 diabetes, and cardiovascular disease. The dietary influence of many African diets (especially grain-base such as millet, maize, brown rice, sorghum, soya, and tapioca) promotes gut lining integrity, immune tolerance towards the microbiota, and its associated immune and inflammatory responses. A fibre-rich diet is a promising biotherapeutic candidate that could effectively modulate inflammatory mediators' expression associated with immune cell migration, lymphoid tissue maturation, and signalling pathways. It could also modulate the stimulation of cytokines and chemokines involved in ensuring balance for long-term microbiome programming. The interplay between host and gut microbial digestion is complex; microbes using and competing for dietary and endogenous proteins are often attributable to variances in the comparative abundances of Enterobacteriaceae taxa. Many auto-inducers could initiate the process of quorum sensing and mammalian epinephrine host cell signalling system. It could also downregulate inflammatory signals with microbiota tumour taxa that could trigger colorectal cancer initiation, metabolic type 2 diabetes, and inflammatory bowel diseases. The exploitation of essential biotherapeutic molecules derived from fibre-rich indigenous diet promises food substances for the downregulation of inflammatory signalling that could be harmful to gut microbiota ecological balance and improved immune response modulation.

Reproductive Indices and Oxidative Stress Biomarkers of Male Wistar Rats Prenatally Exposed to Cigarette Smoke.

The negative influence of cigarette smoking on developing fetus is well documented but reports of prenatal cigarette smoking on male reproductive hormones are controversial. However, shortened anogenital distance (AGD) has been established to be an indicator of potential male infertility. We therefore investigated the effects of prenatal exposure to passive cigarette smoke on AGD, reproductive hormones and oxidative stress biomarkers of Wistar rats. Female rats were randomly divided into two groups (n=5) and cohabited with male. Group 1 was exposed to smoke from an idling cigarette from day 1 of gestation till parturition, while Group 2 served as control (no-exposure). Morphometric variables of the litters were recorded on postnatal day 1 (PND1) and at 6th week postnatal life. The male offspring were then sacrificed by cervical dislocation. Testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were analysed using ELISA. Serum levels of Catalase, sodium dismutase (SOD), malondialdehyde (MDA), lipid profile and liver function biomarkers were examined spectrophotometrically.  On PND1, crown rump length and total body length of rats prenatally exposed to cigarette smoke were significantly shorter. Significantly shorter AGD and crown rump length were also observed at 6th week. Testosterone, LH and FSH were not significantly affected.  Cigarette smoke exposure significantly decreased Catalase and SOD while MDA increased. Liver function biomarkers, HDL and LDL were not affected but serum levels of total cholesterol and triglyceride significantly increased. The observed decline in AGD and precipitation of oxidative stress by intrauterine cigarette smoke exposure may predispose to male infertility at adulthood.