Effects of concurrent chloroquine and ethanol administration on the rat kidney morphology

Introduction: The use of antimalarial chloroquine in malaria-endemic regions of Africa is rampant and it is not uncommon to find individuals taken the drug concurrent with alcohol. Effects of anti-malarial drug chloroquine (Chq) and ethanol (Et) combination on kidney volume and function using rat model was investigated. Methods: 32 adult male rats were randomly distributed into four groups of 8 rats each. Group C serve as control and received vehicle only, while Q is Chq treated only, E is Et treated and QE is Et and Chq treated. Chq was administered intraperitoneally at 1mg/100g body weight weekly and 6% Et in drinking water provided ad libitum. Urine volume was collected before the treatment began and after the treatment. After eight weeks, all animals were euthanized; kidneys were harvested and fixed in 10% neutral formalin. The fixed left kidneys were scanned with computed tomography and the scan slices were used to estimate 3-dimensional kidney volume on ImageJ. Results: Total kidney volume was none significantly increased in Q, E and QE treated compared to control groups (p = 0.5150). Also, microscopic analysis showed increased proximal tubule diameter (p = 0.1426) and epithelial hypertrophy (p = 0.2530) and significant urinary space shrinkage (p = 0.00001). The initial urine volume was not significantly different between the control and treated groups (p = 0.9864) however, following treatment urine volume was significantly reduced in QE rats group (p = 0.0029). Conclusion: The results suggest chloroquine and ethanol combination as potential cause of kidney injury through structural damage and function derangement

Semen quality characteristics of Koekoek breeder cocks influenced by supplemental inclusion levels of onion and garlic mixture at 35-41 weeks of age

ABSTRACT An experiment was conducted to determine the effect of varying dietary supplemental inclusion levels of onion and garlic mixture on semen quality characteristics of Koekoek breeder cocks aged 35-41 weeks. The experimental diets were isocaloric and isonitrogenous but with different supplemental inclusion levels of onion and garlic. A complete randomized design was used for the experiment. The three dietary supplemental levels based on garlic and onion supplemental inclusion levels were Q0 (0 g onion and 0 g garlic per 600 g DM feed), Q1 (2.5 g onion and 2.5 g garlic per 600 g DM feed), and Q2 (5 g onion and 5 g garlic per 600 g DM feed) with each treatment having three replicates. A quadratic type equation was used to determine the onion and garlic levels for optimum semen quality characteristics. Daily supplementation with 5 g onion and 5 g garlic per 600 g DM feed increased progressive motile cells (%), actual life sperm count (×106/nl), and live sperm (%) by 221.20%, 301.51%, and 352.43%, while 2.5 g onion and 2.5 g garlic per 600 g DM feed reduced them by 28.67%, 12.69%, and 19.00%, respectively. However, daily supplementation with 2.5 g onion and 2.5 g garlic per 600 g DM feed increased sperm count (×106/nl) by 12.82%, whereas daily supplementation with 5 g onion and 5 g garlic per 600 g DM feed reduced it by 10.26% in Koekoek breeder cocks. Dietary onion and garlic supplemental inclusion levels of 3.009, 3.191, 4.621, 6.601, 6.719, 2.327, 2.385, and 2.247 g per 600 g DM feed supported optimum progressive motile cells (%), immotile sperm cells (%), actual dead sperm count (×106/nl), actual live sperm count (×106/nl), live sperm (%), acrosome morphology defects (%), acrosome detachment (%), and acrosome swelling (%), with probability values ranging from 0.003 to 0.783, whereas minimum progressive motile cells (%) increase was achieved at an optimum onion and garlic supplementation levels of 3.009 g per 600 g DM feed. These findings have a lot of implications on the use of supplemental onion and garlic inclusion levels to enhance reproductive efficiency in Koekoek breeder cocks

Interactions of alcohol and combination antiretroviral (cART) drug in diabetic male Sprague Dawley rats: Hippocampal perturbations and toxicosis

Hippocampal pathology in diabetes is constantly investigated but the resultant health impact of the concomitant presence of alcohol and combined antiretroviral therapy (cART) in diabetes requires further studies to delineate toxicities inimical to hippocampal normal function. Forty-eight male Sprague Dawley rats were divided into eight groups (n = 6): negative control (NC), alcohol (AL), cART (AV), alcohol-cART (AA), diabetic control (DB), diabetes-alcohol (DAL), diabetes-cART (DAV), and diabetes-alcohol-cART (DAA) exposure groups. Following diabetes induction and sub-chronic (90 days) treatment exposure, hippocampal homogenates were profiled for pro-inflammatory cytokines and oxidative stress (MDA and GPx) using immunoassay, while apoptotic genes (BAX, Bcl2, and Caspase-3), insulin receptor genes (INSR and IRS-1), and blood-brain barrier (BBB) junctional proteins (claudin-5, and occludin) gene expression were assessed using qPCR. Histomorphology of hippocampal neuronal number, nuclei area, and volume of dentate gyrus and neurogenesis were accessed using Giemsa stain, Ki67, and DCX histochemistry respectively. A central hippocampal effect that underpins all treatments is the reduction of DG neuronal number and antioxidant (GPx), highlighting the venerability of the hippocampal dentate gyrus neurons to diabetes, alcohol, cART, and their combinatorial interactions. Additionally, elevated BAX, Bcl2, and IRS1 mRNA levels in the DAL group, and their downregulation in AA, suggests IRS-1-regulated apoptosis due to differential modulating effects of alcohol treatment in diabetes (DAL) in contrast to alcohol with cART (AA). Although the interaction in AA therapy ameliorated the independent alcohol and cART effects on MDA levels, pro-inflammatory cytokines, and DCX, the interaction in AA exacerbated a deficiency in the expression of INSR, IRS-1 (insulin sensitivity), and BBB mRNA which are implicated in the pathogenies of diabetes. Furthermore, the diabetic comorbidity groups (DAV, DAL, and DAA) all share a central effect of elevated hippocampal oxidative stress, BAX, and Caspase-3 mRNA expression with the reduced number of hippocampal neurons, dentate gyrus volume, and neurogenesis, highlighting neurodegenerative and cognitive deficiency implication of these comorbidity treatments. Considering these findings, assessment of hippocampal well-being in patients with these comorbidities/treatment combinations is invaluable and caution is advised particularly in alcohol use with cART prophylaxis in diabetes

Combination Antiretroviral Therapy (cART) in Diabetes Exacerbates Diabetogenic Effects on Hippocampal Microstructure, Neurogenesis and Cytokine Perturbation in Male Sprague Dawley Rats

The increasing incidence of diabetes and HIV/AIDS–diabetes comorbidity in society has led to the prevalence of combination antiretroviral therapy (cART) in diabetes, with some reported neural effects. Therefore, the effects of cART and type two diabetes (T2D) on the hippocampal levels of cytokines, lipid peroxidation; histomorphology and neurogenesis were investigated. Adult male Sprague–Dawley rats were divided into four groups: DB (diabetic rats); DAV (diabetic rats treated with cART (efavirenz, emtricitabine and tenofovir); AV (normal rats treated with cART) and the NC group (with no treatment). Following ninety days of treatment, the rats were terminated, and the brains excised. Immunoassay (IL-1α, IL-6, TNFα and MDA); immunohistochemical (Ki67 and DCX) and cresyl violet histomorphology analyses were carried out on brain homogenates and sections, respectively. In comparison to the control, the results showed that cART significantly elevated the IL-6, TNFα and MDA levels, while DB and DAV significantly reduced the body weight, glucose tolerance, IL-1α, IL-6, TNFα and MDA levels. The hippocampal neuronal number was reduced in AV (dentate gyrus; DG region), in the DB group (Cornu Ammonis subregion 1; CA1 and DG regions only) and in DAV (all three hippocampal regions). Additionally, the expression of neurogenic markers Ki67 and doublecortin (DCX) were reduced in the diabetic group, with a greater reduction in the cART+T2D group compared to the control. Furthermore, the neuronal number at all hippocampal regions was negatively corelated with the diabetic parameters (FBG; fasting blood glucose, NFBG; non-fasting blood glucose, AUC; area under the glucose tolerance curve) but positively correlated with body weight. Additionally, the increase in the DG neuronal nuclei area of DB and DAV was significantly positively correlated with FBG, NFBG and AUC and inversely correlated with the estimated number of neurons and neurogenesis. These findings indicate that cART in diabetes (DAV) has similar effects as diabetes relative to the induction of oxidative stress and impairment of the cytokine immune response, but exacerbated neurotoxicity is observed in DAV, as shown by a significantly decreased DCX expression compared to DB and reduction in the number of Cornu Ammonis subregion 3 (CA3) hippocampal neurons, unlike in cART or the diabetes-alone groups

Atrazine-Induced Hepato-Renal Toxicity in Adult Male <i>Xenopus laevis</i> Frogs

Atrazine (ATZ) is an herbicide commonly detected in groundwater. Several studies have focused on its immunological and endocrine effects on adult Xenopus laevis species. However, we investigated the impact of atrazine on the renal and hepatic biochemistry and histomorphology in adult male frogs. Forty adult male frogs were allocated to four treatment groups (control, one ATZ (0.01 µg/L), two ATZ (200 µg/L) and three ATZ (500 µg/L), 10 animals per group, for 90 days. Alanine aminotransferase (ALT) and creatinine levels increased significantly (p p Xenopus laevis frogs and potentially related aquatic organisms

Atrazine-Induced Hepato-Renal Toxicity in Adult Male Xenopus laevis Frogs

Atrazine (ATZ) is an herbicide commonly detected in groundwater. Several studies have focused on its immunological and endocrine effects on adult Xenopus laevis species. However, we investigated the impact of atrazine on the renal and hepatic biochemistry and histomorphology in adult male frogs. Forty adult male frogs were allocated to four treatment groups (control, one ATZ (0.01 &micro;g/L), two ATZ (200 &micro;g/L) and three ATZ (500 &micro;g/L), 10 animals per group, for 90 days. Alanine aminotransferase (ALT) and creatinine levels increased significantly (p &lt; 0.05) in the 200 and 500 &mu;g/L groups but malondialdehyde only in the 500 &mu;g/L group (p &lt; 0.05). Histopathological observations of derangement, hypertrophy, vascular congestion and dilation, infiltration of inflammatory cells incursion, apoptosis and hepatocytes cell death were observed with atrazine exposure, mostly in the 500 &mu;g/L group. Additionally, histochemical labelling of caspase-3 in the sinusoidal endothelium was observed in all the treated groups, indicating vascular compromise. Evaluation of renal histopathology revealed degradation and atrophy of the glomerulus, vacuolization, thick loop of Henle tubule epithelial cells devolution and dilation of the tubular lumen. Furthermore, expression of caspase-3 indicates glomerular and tubular apoptosis in atrazine-exposed animals. These findings infer that environmentally relevant atrazine doses (low or high) could induce hepatotoxicity and nephrotoxicity in adult male Xenopus laevis frogs and potentially related aquatic organisms