Physiology

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The effect of vitamin B-6 deficiency on copper, zinc and iron balance in the rat.
(1988) Channa, Mahendra Lala.; Burger, F. J.
In order to address the contradictory reports on the rat trace element status during a vitamin 8-6 deficiency, Zn, Cu and Fe balance was assessed over 8 weeks in 3 groups of young male rats. Group 1 was the control group fed on a diet supplemented with 3,5 mg/kg of vitamin B-6. Group 2 was the marginally deficient group, fed a diet supplemented with 1,75 mg/kg of vitamin B-6 and Group 3 was the totally deficient group without any vitamin 8-6 in the diet. Diet, urine and fecal samples were analysed to determine the mean daily Zn, Cu and Fe balance for each group during each week of the study. Urinary xanthurenic acid (XA), plasma pyridoxal (PL), and plasma pyridoxal 5' -phosphate (PLP) were also analysed in order to determine the vitamin 8-6 nutritional status of each animal group. The totally deficient Group 3 showed decreased growth and food consumption when compared to the control and marginally deficient groups. There was a significant difference in XA excretion and plasma PLP and PL levels between all 3 groups with a progressive increase in XA excretion and a progressive decrease in PLP and PL levels from Group to Group 3. Although all groups were found to be in a positive balance for Zn, Cu and Fe, the totally deficient group was in a less positive balance compared to Groups 1 and 2. Furthermore, the percentage excretion of Zn and Cu, when compared to the intake, was greater in this group. This increased excretion, coupled with a decreased food intake, accounted for the lowered Zn and Cu balances in the totally deficient group. Fe excretion did not differ significantly between all 3 groups. The marginally deficient Group 2 showed no significant difference in growth, food consumption, trace element balance and excretion when compared to the control group, indicating the beneficial effects of even subminimal levels of vitamin B-6. This study confirms that the nutritional status of t~ace elements, especially that of Zn and CU, is related to the vitamin B-6 status of the animal.
Effects of moderate treadmill activity on cardiovascular factors in spontaneously hypertensive rats.
(2016) Mwewa, Kibwe.; Nadar, Anand.; Channa, Mahendra Lala.
Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular disease. Oxidative stress due to either increase of reactive oxygen species (ROS) or a compromised antioxidant status has also been positively correlated with cardiovascular diseases. The beneficial effect of physical activity has been well documented in the literature but studies have shown that in the SHR physical activity leads to oxidative stress. The SHR is an excellent model of essential hypertension and hence the present study was designed to investigate the effect of moderate treadmill activity on various cardiovascular factors in SHR. Sixteen male SHR and male Wistar rats (n=16) weighing between 70 and 90 g were used and they were randomly divided into four groups: The SHR exercised group (n=8), Wistar exercised group (n=8), SHR group (n=8) and Wistar (n=8). All the rats in exercised group were subjected to a weekly increase in the rate of activity on the treadmill. Blood pressure, blood glucose and body mass were recorded weekly. At the end of the 8 week experimental protocol, animals were fasted for 12 hours, anaesthetized with halothane and blood and tissue samples harvested. The C-reactive protein (CRP) and antioxidant-associated trace elements such as copper (Cu), iron (Fe), manganese (Mn), selenium (Se), and zinc (Zn) were measured in the blood, brain and skeletal muscle. Cardiotrophin-1 (CT-1) was determined in the plasma, total antioxidant capacity (TAC) and malonyldialdehyde (MDA) were determined in blood and skeletal muscle, plasma TAC levels was also measured. The superoxide dismutase (SOD), IkB and nuclear factor-kappa (NF-kB) gene expression were also measured in skeletal muscle and liver. Kidney sections were stained with Haematoxylin-Eosin (H&E) and sections of aorta were stained with Verhoeff-van Gieson (VVG). The results show that physical activity did not significantly change both the systolic and diastolic blood pressures in SHR. Plasma levels of CRP and NF-kB mRNA expression were increased in both SHR and Wistar exercised groups. An increase in oxidative stress due to physical activity was evident by an increase in TAC and MDA levels in the skeletal muscle. A significant decrease in blood TAC and SOD mRNA expression was also evident in the SHR exercise group. Physical activity also resulted in significant shifts in trace elements that are associated with a compromised antioxidant system.
The effects of multivitamin-multimineral supplementation on the spontaneously hypertensive rat model of hypertension.
(2015) Höfler, Rosemarie Ursula.; Channa, Mahendra Lala.
ABSTRACT The nutraceutical industry has proliferated in recent years with the most popular form of supplementation being the multivitamin-multimineral (MVMM) supplement. In the animal health sector, supplement use has also expanded. The objective of this study was to determine the effects of MVMM supplementation, beneficial or otherwise, on the general health status of the spontaneously hypertensive rat (SHR) strain, an animal model used in hypertension research. A commercially prepared MVMM supplement was given tri-weekly via oral dosing for eight weeks to two groups of seven adult female SHR and Wistar rats. Their corresponding control groups were dosed with deionised water only. Systolic and diastolic blood pressure, fasting blood glucose, growth rate and food and water intake were measured weekly. At the end of eight weeks, the animals were euthanized and a full blood profile, urine sodium potassium ratio, blood urea nitrogen levels and total plasma cholesterol was measured for all groups. Further biochemical tests included determining plasma C-reactive protein, angiotensin-converting enzyme and kidney lipid peroxidation levels. Blood and tissue trace element profiles were determined by ICP and EDX analysis. A histological study was conducted on the kidney and aorta. MVMM supplementation had significant metabolic, cardiovascular and renal effects in the SHR group. It increased growth and caused a significant reduction in the diastolic blood pressure of both SHR S and WIS S groups over the eight week period. It also lowered total cholesterol and increased RBC count in the SHR S group. Supplementation also had some renoprotective properties as the SHR S group exhibited lesser hypertension related morphological changes in the kidney due to lowered blood pressure and possible antioxidant effects of the supplement. This was however not translated into any improvement in renal function. No adverse effects on the general health status of the animals were observed. MVMM supplementation may therefore be useful in aiding growth and delaying the onset of hypertension and the related complications. It may also assist in the longevity of the breeding stock of SHR rats.
Evaluation of the potential benefits of L-ergothioneine on selected complications associated with type-2 diabetes in a rat model.
(2021) Dare, Ayobami.; Nadar, Anand.; Channa, Mahendra Lala.
Several pathogenic factors promote type-2 diabetic complications in patients, including cardiomyopathy, nephropathy, and non-alcoholic fatty liver disease (NAFLD). Specific nutraceuticals from food may act as a medicinal adjuvant in managing diabetic complications. L-ergothioneine (L-egt), a bioactive compound obtained from medicinal mushrooms, beans and some meat products, has been shown to reduce lipid accumulation, provide cytoprotection in tissue injury and enhances therapeutic efficacy when used as adjuvant. This study investigated the effect of L-ergothioneine with or without metformin on pathogenic metabolic pathways and biomarkers associated with selected diabetic complications in a type-2 diabetic rat model. Ninety (90) adult male Sprague-Dawley (175±20)g rats were divided into three study groups [study 1 (36), study 2 (30) and study 3 (24)]. A 10% fructose solution was provided ad libitum to adult male Sprague- Dawley (175±20)g rats for 14 days followed by a single intraperitoneal injection of low dose streptozotocin (STZ 40mg/kg bwt, i.p) to induce type-2 diabetes after which the animals were randomly divided into six, five, and four groups (n=6) in studies 1 (liver), 2 (kidney), and 3 (heart), respectively. The control groups were administered 1ml/100g distilled water, while L-egt (35mg/kg bwt), metformin (500mg/kg bwt), and losartan (20mg/kg bwt) were administered in the other groups. At the end of each study, animals were euthanized via decapitation, blood samples were collected, while the heart, kidney, and liver tissue were excised and used for biochemical, RT-qPCR, ELISA, western blotting, and histopathological analysis. An in-silico study was done to evaluate the molecular antioxidant mechanism of L-egt. Administration of L-egt, with or without metformin, to diabetic animals positively altered selected biomarkers of hepatic, renal, and cardiac dysfunction and prevented structural damage in these tissues. This treatment regimen mitigated oxidative stress, inflammation, and fibrosis by downregulating (p<0.05) SREBP1c, FAS, NF-kB, fibronectin, TGFβ1, and Keap1 expression and upregulating (p<0.05) Nrf2, Sirt1, NQO1, and HO1 expression compared with the diabetic control animals. Interestingly, co-administration of L-egt and metformin improved glucose homeostasis and reduced HOMA-IR. The in-silico study showed that L-egt binds to the active site of Nrf2 and may serve as a ligand to activate this potent antioxidant molecule. The overall result from this study showed the potential benefits of L-ergothioneine in the management of selected complications associated with type-2 diabetes. This bioactive compound may be an effective adjuvant to attenuate hypertriglyceridemia, oxidative stress, and inflammation, thereby protecting vital organs associated with diabetic complications against injury and improving glycemic control when coadministered with metformin to delay the onset of diabetic complications.
Impact of quercetin-3-0-rutinoside on biochemical and reproductive profile of rats prenatally exposed to high fat diet.
(2020) Adeyemi, Toluwalope Esther.; Nadar, Anand.; Channa, Mahendra Lala.
The increasing prevalence of infertility and obesity over the last few decades have become a major public health challenge among individuals within the reproductive age. Consumption of a high-fat diet (HFD) is a harbinger for many metabolic alterations and diseases including infertility and subfertility. Studies have shown that the reproductive health of an individual can be programmed prior birth since exposure to certain environmental factors especially during intrauterine life play significant roles in transcriptional and epigenetic alterations in pivotal genes. However, understanding the molecular mechanisms linking oxidative stress caused by adverse environmental conditions to intrauterine alterations at critical periods of development might help in the clinical management of diet-induced infertility problems. This study therefore aimed at investigating the impact of maternal HFD consumption on sex-linked differences in the reproductive hormone profiles of diet unexposed offspring and examined the therapeutic potential of 150 mg/kg Quercetin-3-O-rutinoside (QR) against the HFD-induced biological changes. Adult female Sprague Dawley rats were randomly divided into two groups and fed either 45% HFD or normal diet (ND) for eight weeks before mating with male rats fed ND. Thereafter, the pregnant rats were divided into four dietary treatment groups: ND, HFD, ND+QR, and HFD+QR. At gestation day 19 (GD19), n=7 animals per group were sacrificed. Blood and tissue samples were collected and stored at -800C for biochemical and molecular analyses. The remaining dams were allowed to litter naturally and sacrificed. The pups were also sacrificed at postnatal day (PND) 21, 28 and 35. Blood and tissue samples were collected and stored for subsequent analyses. Using standard laboratory procedures, we measured oxidative changes in the liver, placenta and brain tissues by assessing levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase and nitric oxide (NO). Concentrations of hypothalamic gonadotropin releasing hormone (GnRH), serum luteinizing hormone (LH), testicular testosterone, and brain tumour necrosis factor (TNF-α) and glucagon-like peptide 1 (GLP-1) were assessed via enzyme linked immunosorbent assay (ELISA) technique. HFD-induced transcriptional changes in chemerin, chemokine-like receptor (CMKLR 1), TNF-α, GLP-1, interleukin-1 (IL-1β) and nuclear factor kappa B (NFκB) in the hypothalamic and testicular tissues were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). After eight weeks of maternal HFD consumption, lipogram test indicated decreased plasma total cholesterol (TC) level, hypertriglyceridemia and increased low-density lipoprotein (LDL) levels. Our findings also showed that offspring of HFD-fed dams had delayed fur appearance and lower body weight compared to those from the control (ND) dams. These morphological changes were accompanied by elevated MDA levels in placenta, liver and brain tissues of HFD-fed dams and their diet-naïve offspring. Furthermore, there was evidence of hepatic nitrosative stress, time-dependent and sex-linked differences in hepatic SOD and brain GSH levels in the offspring. Also, hypothalamic GnRH and serum LH levels were significantly reduced at PND 28 and 35 in the offspring. Moreover, testicular testosterone was decreased at PND 35 in offspring of HFD-fed dams. Upregulation of chemerin, TNF-α, IL-1β mRNA transcripts in the hypothalamic-gonadal axis of male offspring indicates possible HFD-induced tissue inflammation and consequences for dysregulated steroidogenic and/or reproductive functions. Elevated brain GLP-1 may be linked to activated bioenergetic and homeostatic responses to HFD-induced oxidative stress. Overall, maternal HFD exposure led to induced oxidative stress, low-grade tissue inflammation and decreased levels of gonadotropins and androgens in their diet naïve offspring, whereas QR has little or no significant effects on these parameters.
Insulin resistance and salt sensitivity in the rat model of hypertension
(2002) Channa, Mahendra Lala.; Somova, Liliana I.
Abstract available in PDF file.

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