Effect of silymarin on blood coagulation profile and osmotic fragility in carbon tetrachloride induced hepatotoxicity in male Wistar rats.

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.

Dietary Supplementation with D-Ribose-L-Cysteine Prevents Hepatic Stress and Pro-Inflammatory Responses in Male Wistar Rats Fed a High-Fructose High-Fat Diet.

Diets rich in fats and fructose are associated with the pathogenesis of oxidative stress-induced non-alcoholic fatty liver disease. Therefore, we investigated the effect of D-ribose-L-cysteine (DRLC) in high-fructose high-fat (HFHF) diet-fed rats. Twenty rats (n = 5), divided into four groups, were simultaneously exposed to HFHF and/or DRLC (250 mg/kg) orally during the 8 weeks of the study. Results showed that HFHF precipitated pro-inflammation and selective disruption of the oxidative stress markers. There were significant decreases in the level of antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), hepatic SOD and GPX. Significant increases in serum levels of uric acid (UA), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and hepatic Xanthine oxidase (XO) were observed in the HFHF compared to the control. In the HFHF + DRLC group, oxidative stress was mitigated due to differences in serum levels of SOD, GPX, TAC, TNF-α, liver SOD, and XO relative to control. The administration of DRLC alone caused significant reductions in malondialdehyde, UA and CRP and a significant increase in SOD compared to the control. DRLC prevents hepatic and systemic oxidative stress and pro-inflammatory events in HFHF diet-fed rats.

Angiotensin converting enzyme inhibitor potentiates the hypoglycaemic effect of NG-nitro-L-arginine methyl ester (L-NAME) in rats.

The inhibition of renin angiotensin system pathway has been largely documented to be effective in the control of cardiovascular events. The present study investigated the effect of angiotensin converting enzyme (ACE) inhibitor on fasting blood glucose level in hypertension induced by the inhibition of nitric oxide synthase (NOS) in male Wistar rats. Hypertension was induced by the inhibition of NOS using a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). The blockade of NOS resulted in an increase in blood pressure, ACE, angiotensin II and endothelin-1 levels, and a decrease in fasting blood glucose and nitric oxide (NO) levels. The hypertensive rats treated with ACE inhibitor (ramipril) recorded a decrease in blood pressure, ACE, angiotensin II, endothelin-1, NO and fasting blood glucose levels, and an increase in prostacyclin level. In conclusion, ACE inhibitor potentiated the hypoglycaemic effect of NOS inhibitor and this effect is independent of NO and pancreatic insulin release.

Maternal hypothyroidism prolongs gestation period and impairs glucose tolerance in offspring of Wistar rats.

OBJECTIVES: Pregnancy is a critical period keenly regulated by both maternal and foetal factors and a shift in these factors could result in severe complications manifesting in foetal and adult life. However, maternal hypothyroidism before and/or during pregnancy is a critical factor. This study investigated the effect of maternal hypothyroidism on glucose tolerance and thyroid function in male and female offspring. METHODS: Fifteen adult female Wistar rats were divided into three groups: Group 1 (sham-control), Group 2 (thyrodectomized) and Group 3 (thyroidectomised + L-thyroxine treated). Blood thyroxine (T4) level was measured on the day 10 after thyroidectomy in Groups 1 and 2, and day 35 in Group 3. Males were introduced to the female rats after T4 measurement. At PND-112, T4 levels of their offspring were measured. Oral Glucose Tolerance Test (OGTT) was measured in offspring at PND-133. RESULTS: Thyroxine reduced significantly in Group 2 and their offspring (male and female) compared to Group 3 while gestation period was prolonged significantly in Group 2 compared to Group 1. Hypothyroid male offspring showed depressed glucose tolerance, however, no effect was observed in female offspring. CONCLUSIONS: This study suggests that maternal hypothyroidism prolonged gestation period, induced foetal hypothyroidism in both genders and depressed glucose tolerance in male offspring.

Cardiovascular Responses to Squatting Postural Stress among Non-Diabetic and Type-2 Diabetic Nigerian Black Africans.

Background: A change in posture brings about a significant alteration in cardiovascular functions. The squat test has been used to study autonomic function in White Europeans but not Black Africans. The aim of this study is to determine the cardiovascular effects of postural stress in Black African non-diabetics and Type-2 diabetics. Method: Blood pressure (BP) and heart rate (HR) was measured in 40 non-diabetics and 40Type-2 diabetics in sitting, standing from sitting, squatting and standing from squatting positions Difference in BP and HR between consecutive positions was tested using 2- way mixed ANOVA. Proportions of those who showed orthostatic hypotension and hypertension were compared with Fishers exact test. Significance was set at p <0.05. mmHg Δ: BP and HR changes evoked by standing from sitting were not different, however squatting evoked greater increase in BP in diabetics(change (Δ) SBP: 5.85±9.95 vs 17.40±13.75mmHg: Δ DBP: 0.15 ± 6.89 vs 5.10 ± 7.59 mmHg:Δ MABP:2.02 ± 6.98 vs 8.63 ± 9.34 mmHg ,p <0.05) and standing from squatting evoked greater fall BP in diabetics (ΔSBP: -9.80±13.89 vs -24.35±16.03 mmHg; Δ MABP:-2.02±6.98 vs -8.63±9.34 mmHg: Δ PP: -2.28 ±15.35 vs -14.50 ±11.96 mmHg, p < 0.05) while Δ HR did not differ. A higher proportion of diabetics showed SBP and DBP orthostatic hypertension. Conclusion: Relative to the non-diabetics, diabetics showed greater BP but not HR responses to postural stress.

D-ribose-L-cysteine prevents oxidative stress and cardiometabolic syndrome in high fructose high fat diet fed rats.

Cardiometabolic syndrome has been linked with dietary modification. Therefore, we investigated the effects of D-ribose-L-cysteine (DRLC) in rats fed with high fructose high fat (HFHF) diet. Twenty rats (n = 5), divided into 4 groups were concurrently exposed to HFHF and/or DRLC (250 mg/kg, p.o) during the 8 weeks study. The result showed that compared to control group, HFHF group had significant impairment in lipid and glucose homeostasis, increased cardiac xanthine oxidase, systolic blood pressure, heart rate, %body weight change and fluid intake. Also, there were significant reductions in HDL-C, cardiac (GPX, NO&GGT), feed intake and relative heart weight in the latter, relative to the former. However, there were no significant differences in most of the observed physical and biochemical changes in HFHF + DRLC group compared to control. DRLC alone did not disrupt the level of biomarkers. Conclusively, DRLC prevented the manifestation of oxidative stress and cardiometabolic syndrome in HFHF-diet fed rats.

Changes in antioxidants status, atherogenic index and cardiovascular variables after prolonged doses of D-ribose-L-cysteine in male Wistar rats.

D-ribose-L-cysteine (DRLC) acts as a rate limiting substrate for the synthesis of glutathione (GSH). GSH deficiency has been linked to oxidative stress, hypertension and cardiovascular diseases. There are limited findings on the effects of DRLC in the physiologic state. This study was therefore designed to investigate cardiovascular effects of different doses of DRLC in normal Wistar rats. Fifteen male Wistar rats were assigned into 3 groups (n = 5). Group 1 was administered orally with 10 mg/kg distilled water (Control). Groups 2 and 3 were administered orally with DRLC 125 mg/kg and 250 mg/kg respectively daily for 8 weeks, respectively. Animals were weighed; blood pressure and heart rate measured using rat tail cuff method. They were euthanized, blood collected and organs harvested. Serum C-reactive protein (CRP) was determined through ELISA. Gamma glutamyl transferase (GGT), heart GSH, glutathione peroxidase (GPx), total thiol and lipid profile and were assessed through spectrophotometry. Data were expressed as mean ± SEM and compared by ANOVA at P < 0.05. DRLC 250 significantly increased total thiol, GSH and GPx in heart tissues but decreased GGT, atherogenic index and CRP in normal male Wistar rats compared to DRLC 125 and control. DRLC supplementation in normal male Wistar rats may sustain cardio functions and decrease atherogenicity.

Evaluation of heart rate variability, blood pressure and lipid profile alterations from dual transceiver mobile phone radiation exposure.

OBJECTIVES: Electromagnetic fields have been reported to alter electrical activities in the brain and heart. However, there is paucity of information on the potential functional alterations that magnetic fields from mobile phone could cause to the heart. This study investigated heart rate variability (HRV), blood pressure (BP) and lipid profile in Wistar rats exposed to electromagnetic field radiation from a dual transceiver mobile phone (DTrMP). METHODS: Twenty-one male albino Wistar rats (140-180 g) were randomly assigned to two major groups positioned 5 m apart as follows: control: no phone (n=7) and treatment group (n=14) continuously exposed to electromagnetic field from Tecno T312 DTrMP 900/1800 MHz set in silence mode. Experimental treatment consisted in 10 min calls/day, directed to this device for a period of six weeks. Seven animals from the treatment group were allowed to recover for a period of two weeks after exposure. HRV, systolic, diastolic and mean arterial BP were noninvasively investigated, while serum lipid profile and heart tissue nitric oxide (NO) activities were determined using standard procedures. RESULTS: There was significant (p<0.05) increase in systolic, diastolic, mean arterial BP and a decrease in HRV. Serum high density lipoproteins decreased, while total cholesterol, atherogenic indices, and heart NO levels increased significantly in the radiation exposed animals. The alterations observed in exposed animals remained unchanged even after the recovery period. CONCLUSIONS: These results suggest that exposure to electromagnetic radiation from dual transceiver mobile phones could be a risk factor to increase in blood pressure.

Co-administration of prazosin and propranolol with glibenclamide improves anti-oxidant defense system in endothelial tissue of streptozotocin-induced diabetic Wistar rats.

Background Due to increasing prevalence of diabetes and associated endothelial dysfunction, this study was carried out to investigate the effects of co-administration of adrenoceptor blockers (prazosin and propranolol) and glibenclamide on plasma biomarkers of endothelial functions in diabetic rats. Methods Experiments were carried out on 35 male Wistar rats (170-200 g). They were divided into seven groups (n=5) as follows: normal control, diabetic control, diabetic + glibenclamide (GLB-5mg/kg/day), diabetic+ prazosin (PRZ-0.5 mg/kg/day), diabetic + PRZ + GLB, diabetic + propranolol (PRP-10 mg/kg/day), diabetes + PRP + GLB. Experimental diabetes was induced with streptozotocin (60 mg/kg) and drugs were administered orally for 3 weeks. Blood pressure was measured and animals were sacrificed afterwards. Blood samples were collected by cardiac puncture, and major marker of endothelial functions, nitric oxide derivatives (NOx), as well as superoxide dismutase (SOD) and malondialdehyde (MDA) were measured on the plasma. The aorta was harvested for histological examination. Data were subjected to descriptive statistics and analysed using ANOVA at α 0.05. Results There was a significant increase in levels of NOx and SOD, and a decrease in MDA level in diabetic treated groups compared to diabetic control. Mean blood pressure increased in diabetic control and diabetic + GLB group when compared with normal control, while it was mildly reduced in diabetic group treated with PRZ and PRP, and co-administered GLB. More so, Aorta histology was altered in diabetic control groups when compared with normal control and all diabetic treated groups. Conclusions Results from this study suggest that PRZ, PRP, and GLB (singly and in combined therapy) could have a restorative effect on endothelial functions in diabetes.

Anti-lipidemic Effect of Fractions of Peristrophe bivalvis Leaf in NG-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats.

PURPOSE: The reduction in nitric oxide (NO) bioavailability accelerates atherosclerosis development, augments lipolysis, elevates blood pressure and upregulate leukocyte level. This study was designed to examine the biochemical constituents of fractions of Peristrophe bivalvis (PB) leaf, their effect on blood pressure, serum lipid contents and complete blood count in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHOD: Male Wistar rats were grouped into control and hypertensive groups. The hypertensive group was pretreated with 60 mg/kg b.w of L-NAME (L-NAME60) daily for two weeks. They were then randomly sub-grouped into: Hypertensive (H), Hypertensive+n-hexane fraction (HHF), Hypertensive+dichloromethane fraction (HDF), Hypertensive+ethyl acetate fraction (HEF) and Hypertensive+aqueous fraction (HAF) groups. These were orally gavaged with L-NAME60 and L-NAME60+200 mg/kg b.w of fractions of PB respectively, daily for two weeks. RESULT: The biochemical components analysis of the fractions of PB identified numerous polar and non polar compounds like alkaloids, organic acids and esters. The results showed a significant increase in NO level in HHF and HEF groups compared to H. Total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C) and very LDL-C were significantly decreased in HAF group compared to H. High density lipoprotein cholesterol (HDL-C) increased significantly and atherogenic indices decreased significantly in HHF, HDF and HAF groups compared to H, while reduced glutathione level increased significantly in HHF group compared to H. White blood cells count effectively decreased in HEF group compared to H. CONCLUSION: In brief, the fractions of PB leaf increased HDL-C and NO, and decrease atherogenic indices in L-NAME treated rats.

Peristrophe roxburghiana leaf extracts exhibited anti-hypertensive and anti-lipidemic properties in L-NAME hypertensive rats.

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.

Reduction in nitric oxide bioavailability shifts serum lipid content towards atherogenic lipoprotein in rats.

Nitric oxide (NO) is major endothelial relaxing factor and reduction in its bioavailabilty has been linked to hypertension. Furthermore, high lipid content is a strong risk factor predisposing to cardiovascular diseases. The principal focus of this study was to investigate the effect of blockade of nitric oxide synthase (NOS) on serum lipid content in rats. Male Wistar rats (150-170 g, n = 15) were randomly divided into two groups designated control (n = 5), and L-Name group (n = 10) and were gavage with distilled water and 60 mg/kg of L-NAME respectively daily for three weeks. After 3 weeks, the L-NAME group was sub-divided into two sub-groups (n = 5 each): L-NAME (60 mg/kg of L-NAME), and L-NAME plus ramipril (LR) (60 mg/kg of L-NAME plus 20 mg/kg of ramipril) and were treated daily for another three weeks. The blood pressure (BP) of the conscious rats was measured by tail-cuff method at the onset, at the third and at the sixth weeks of the experiment; while serum lipid contents and NO were measured at the third and sixth weeks. At the end of the experiment blood sample was drawn by ocular puncture for evaluation of lipid profile and NO, and the animals were later euthanized by overdose of anaesthesia. Data were analyzed using ANOVA at p < 0.05. There was a significant increase in BP, triglyceride, total cholesterol, low density lipoprotein-cholesterol, and atherogenic indices in L-NAME group compared to the control and LR group (p < 0.05); NO and high density lipoprotein-cholesterol was significant lower in the L-NAME group compared to control and LR (p < 0.05). In conclusion, reduction in NO bioavailability alters lipid metabolism, which was rectified by ramipril.

Male Sexual Dysfunction, Leptin, Pituitary and Gonadal Hormones in Nigerian Males with Metabolic Syndrome and Type 2 Diabetes Mellitus.

BACKGROUND: Pituitary and gonadal dysfunctions resulting from increased adiposity leading to disturbances of sexual and reproductive functions have been reported in males with metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). The aim of this study was to evaluate sexual dysfunction, leptin, and reproductive hormones in Nigerian males with MS and DM2. METHODS: Participants were 104 men (34 males with DM2, 17 men with MS and 53 men with normal body mass index (18.5-24.9 Kg/m (2)) without MS (controls)). The International Diabetes Federation (2005) criteria were used for MS diagnosis. Reproductive history, anthropometry, blood pressure (BP) and 10 ml fasting blood samples were obtained by standard methods. Fasting plasma glucose, total cholesterol, triglycerides and high density lipoprotein cholesterol were determined by enzymatic methods while low density lipoprotein cholesterol was calculated. Leptin, follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin, testosterone and oestrogen were determined by enzyme immunoassay (leptin by Diagnostic Automation, Inc.; others by Immunometrics (UK) Ltd.) while oestrogen-testosterone ratio was calculated. Data analyzed using ANOVA, Chi square and multiple regression were statistically significant at p<0.05. RESULTS: Testosterone was significantly lower in MS than controls while oestradiol and ETR were significantly higher in MS compared with controls and DM2 group (p<0.05). ETR significantly predicted testosterone in all groups (p<0.05). Significantly lower libido was observed in men in MS than controls and DM2 groups (p<0.05). CONCLUSION: Sexual and reproductive dysfunction may be related to increased conversion of testosterone to oestrogen in increased adipose mass in men with metabolic syndrome and type 2 diabetes mellitus.

Effects of Hypothyroidism and Exogenous Thyroxine on Gastrointestinal Organs of Rat.

Thyroxine (T4) is important in gut development and maturation, and its use in treating hypothyroidism is becoming more popular. This study was conducted to evaluate the effect of thyroidectomy and thyroxine replacement on some gastrointestinal organs. Ten out of 20 thyroidectomised rats received 100pg/kgbw of T4 for five weeks to become euthyroid while the rest were left to become hypothyroid. Ten sham operated rats were made hyperthyroid by giving 100pg/kg.bw of T4 for five weeks, while the other ten sham operated rats served as control. 10mg/kg.bw intraperitoneal injection of ketamine was given as anesthesia for thyroidectomy and sham operation. At the end of the fifth week, the animals were sacrificed. Liver, stomach and small intestine were harvested and their morphological dimensions measured. Everted sacs were made from the small intestine for glucose transfer studies and slides for histomorphometry. There was no significant difference in the weights of the liver and stomach of the groups when compared with the control group. There was significant increase in length and diameter but reduced wall thickness in the hyperthyroid small intestine; unlike that of hypothyroid which had significant  shorter length, decreased diameter but increased wall thickness. Villi length and crypt depth was higher in hyperthyroid  but smallest in the hypothyroid. Glucose transfer was lesser in the hypothyroid but greater in the hyperthyroid intestine. These findings show that hypothyroidism diminishes the morphological variables of absorption in the small intestine as a mechanism to reducing its transfer capacity, while thyroxine replacement increases these variables as mechanism to increasing intestinal transfer capacity.