Khaled Al-Qattan

Anti-diabetic and hypolipidaemic properties of ginger ( Zingiber officinale ) in streptozotocin-induced diabetic rats

In the present study, the hypoglycaemic potentials of ginger (Zingiber officinale) were studied in rats. An aqueous extract of raw ginger was administered daily (500 mg/kg, intraperitoneally) for a period of 7 weeks to streptozotocin (STZ)-induced diabetic rats. Fasting blood serum was analysed for blood glucose, cholesterol and triacylglycerol levels. The STZ-injected rats exhibited hyperglycaemia accompanied with weight loss, indicating their diabetic condition. At a dose of 500 mg/kg, raw ginger was significantly effective in lowering serum glucose, cholesterol and triacylglycerol levels in the ginger-treated diabetic rats compared with the control diabetic rats. The ginger treatment also resulted in a significant reduction in urine protein levels. In addition, the ginger-treated diabetic rats sustained their initial weights during the treatment period. Moreover, ginger decreased both water intake and urine output in the STZ-induced diabetic rats. The present results indicate that raw ginger possesses hypoglycaemic, hypocholesterolaemic and hypolipidaemic potential. Additionally, raw ginger is effective in reversing the diabetic proteinuria observed in the diabetic rats. Thus, ginger may be of great value in managing the effects of diabetic complications in human subjects.

Garlic Increases Antioxidant Levels in Diabetic and Hypertensive Rats Determined by a Modified Peroxidase Method

Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes and hypertension. In the present study, the total antioxidant status in diabetic and hypertensive rats before and after treatment with garlic (Allium sativum) was determined. The total serum antioxidants were measured by a modified method reported earlier by Miller and coworkers. The reproducibility of the assay was confirmed by determining standard curves for the known antioxidants: trolox (a stable analog of vitamin E), glutathione and vitamin C with interassay correlation coefficients (R2, n = 10 in triplicate) of 0.9984, 0.9768 and 0.987, respectively, confirming the reliability and reproducibility of the assay. This assay was then used to determine total serum antioxidant levels of streptozotocin-induced diabetic rats and two-kidney one-clip hypertensive rats both before and after 3 weeks of treatment with an aqueous extract of garlic (500 mg/kg IP daily). The serum antioxidant levels of rats after 3 weeks of treatment were significantly higher (P < .001) than the pretreatment levels in both diabetic and hypertensive rats. The increased serum antioxidant levels were paralleled by a decrease in serum glucose in the garlic-treated diabetic rats and lowered systolic blood pressure in the garlic-treated hypertensive rats. We conclude from our study that (i) total antioxidants can be measured by a simple, reproducible, reliable assay and (ii) the total antioxidant status can be significantly improved by treatment with garlic.

Including Garlic in the Diet May Help Lower Blood Glucose, Cholesterol, and Triglycerides

Raw and boiled aqueous extracts of garlic (Allium sativum) were administered daily to normal rats both orally and intraperitoneally for 4 wk. The serum levels of glucose, cholesterol, and triglycerides were measured. When the rats were treated with a low dose (50 mg/kg) of raw aqueous extract of garlic, no significant changes in the serum glucose levels were observed compared with the control group. However, there was a significant reduction in the cholesterol level of rats receiving a low dose of garlic (11-14%). Rats receiving garlic orally and intraperitoneally also showed a significant reduction in triglyceride levels (38%). When the rats were treated with a high dose (500 mg/kg) of raw garlic, glucose, cholesterol, and triglyceride levels were significantly affected. When boiled garlic extracts were administered at high concentrations (500 mg/kg), there was no effect on the level of serum glucose. However, a relatively small but significant decrease in the concentration of cholesterol and triglycerides was observed in the serum of the rats receiving boiled garlic. Raw garlic had a profound effect in reducing the glucose, cholesterol, and triglyceride levels, whereas boiled garlic had little effect in controlling these parameters. Therefore because hyperlipidemia is a major etiopathological factor for atherosclerosis, garlic may play an important role in the prevention of atherosclerosis.

Nitric Oxide Mediates the Blood-Pressure Lowering Effect of Garlic in the Rat Two-Kidney, One-Clip Model of Hypertension

Garlic reduces blood pressure (BP) in two-kidney, one-clip (2K-1C) rats, and enhances nitric oxide (NO) synthesis in in vivo and in vitro experiments. NO is an important modulator of BP in the 2K-1C model. This study investigated the role of NO in the BP-lowering effect of garlic in the 2K-1C model. BP readings (mm Hg) were obtained from 2K-1C rats in 4 groups treated intraperitoneally for 2 wk with either normal saline (NS), garlic, L-nitroarginine-methylester (L-NAME), or L-NAME+garlic (n=4x5). BP was determined using the tail-cuff method and compared with data of 4 similarly treated groups of normal (unclipped) rats (NRs). The BP readings of NR groups were 120+/-3 mm Hg for the NS-treated group, 120+/-2 mm Hg for the garlic-treated group, 167+/-3 mm Hg for the L-NAME treated group (higher than NS or garlic, P<0.001) and 128+/-5 mm Hg for the garlic+L-NAME-treated group (lower than L-NAME, P<0.001). The BP readings of 2K-1C rat groups were: for the NS group, 169+/-6 mm Hg (higher than NRs, P<0.001); for the garlic group, 116+/-7 mm Hg (lower than NS, P<0.001); for the L-NAME group: 184+/-8 mm Hg (higher than garlic, P<0.001), and for the L-NAME+garlic group: 130+/-6 mm Hg (lower than garlic or NS, P<0.001). The data show that L-NAME increases the BP of both NRs and 2K-1C rats, with the rise more evident in the NRs (39 vs. 9%, respectively). Garlic counteracts the hypertensive effect of L-NAME in NRs as well as 2K-1C rats. We conclude that the BP-lowering effect of garlic in the rat 2K-1C model may be partly mediated through the NO pathway.

Anti-diabetic and anti-oxidant potential of aged garlic extract (AGE) in streptozotocin-induced diabetic rats

BackgroundAlthough aged garlic extract (AGE) shares some active components with fresh garlic and in spite of its palatability and milder side effects, the anti-diabetic and related anti-oxidant properties of AGE have not been investigated extensively, and the reported findings are inconsistent.This study investigated the anti-diabetic effects of 3 incremental doses of AGE in streptozotocin (STZ)-induced diabetic rats (fasting blood sugar > 20 mM).MethodDiabetic rats were divided into a control diabetic group (CD) and AGE-treated diabetic group (AGE-D). The AGE-D was divided into 3 groups and accordingly treated with AGE i.p. at 100, 300 and 600 mg/kg daily for 8 weeks. A control normal group (CN) was also included for reference.ResultsCompared to the CN group, the CD group showed significant loss of body weight (over 50 %); and decreased serum insulin concentration (10 fold) and total anti-oxidant level and catalase activity (45–70 %) in serum, kidney and liver. Conversely, the CD rats had an elevated blood glucose (nearly 4 fold), serum cholesterol (nearly 2 fold) and triglycerides (>2 fold), erythrocyte glycated hemoglobin (GHb, 3 fold) and kidney and liver lipid peroxidation (MDA levels). Treatment with AGE positively reversed the diabetic changes in the targeted parameters to levels significantly lower than those measured in the CD group and the degrees of attenuation were almost dose dependent especially with the two higher doses.ConclusionAGE exhibits a dose-dependent ameliorative action on indicators of diabetes in STZ-induced diabetic rats.

Green Tea Attenuates Oxidative Stress and Downregulates the Expression of Angiotensin II AT1 Receptor in Renal and Hepatic Tissues of Streptozotocin-Induced Diabetic Rats

This study investigates the potential of green tea to modulate oxidative stress and angiotensin II AT1 receptor expression in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (diabetic control), and green-tea-treated diabetic rats. Total antioxidant, catalase, and malondialdehyde levels were assayed by standard procedures. Levels of AT1 receptor labeling, in renal and hepatic tissues of the three rat groups, were immunohistochemically investigated using an anti-AT1 receptor antibody. Levels of total antioxidant and catalase were significantly reduced, whereas malondialdehyde levels and AT1 receptor labeling were significantly increased in renal and hepatic tissues of diabetic control rats compared to normal rats. Compared to diabetic control rats, total antioxidant and catalase levels were significantly increased, whereas malondialdehyde levels and AT1 receptor labeling in the green-tea-treated diabetic group were significantly reduced throughout hepatic lobules and renal cortical and medullary vascular and tubular segments to levels comparable to those observed in normal rats. The capacity of green tea to modulate diabetes-induced oxidative stress and AT1 receptor upregulation may be beneficial in opposing the deleterious effects of excessive angiotensin II signaling, manifested by progressive renal and hepatic tissue damage.

Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders.

Garlic (Allium sativum) attenuate glomerular glycation in streptozotocin-induced diabetic rats: A possible role of insulin

OBJECTIVE This study investigated the effect of fresh garlic aqueous extract on glomerular glycation in streptozotocin-induced diabetic rats. METHOD Serum insulin and glucose, in addition to renal corpuscles and erythrocyte hemoglobin glycation were determined in normal saline-treated normal rats (NS-NR), normal saline-treated diabetic rats (NS-DR) and garlic-treated diabetic rats (G-DR). RESULTS Compared to NS-NR, NS-DR showed significant decrease in serum insulin and increase in serum glucose and hemoglobin glycation. NS-DR also showed intense, diffused glomerular periodic acid Schiff activity. Compared to NS-DR, G-DR showed significant increase in serum insulin and decrease in serum glucose and hemoglobin glycation. Furthermore, the G-DR glomerular periodic acid Schiff activity and distribution was almost restored to that observed in NS-NR. CONCLUSION Garlic may attenuate glomerular glycation in streptozotocin-induced diabetic rats. This effect could be partially mediated via euglycemia induced by revitalization of endogenous insulin.

Altered Expression of Na+/H+ Exchanger Isoforms 1 and 3 in Clipped and Unclipped Kidneys of a 2-Kidney-1-Clip Goldblatt Model of Hypertension

Background: Functional differences between the clipped and unclipped kidneys in a 2-kidney-1-clip (2K-1C) hypertension model have been reported. However, the molecular basis of these changes is poorly understood. Objectives: Expression of NHE-1 and NHE-3 isoforms and sodium pump activity (PNP), and their modulation by blood pressure (BP), PGE2 and TXB2 were examined in the kidneys of 2K-1C rats treated with cilazapril for short- (4 and 24 h) and long-term (7 days) periods. Methods: 2K-1C rats were divided into two groups. Group 1 (short-term) animals were treated with a single dose of cilazapril for 4 or 24 h. Group 2 (long-term) animals received a daily dose of cilazapril for 7 days. 2K-1C animals receiving water served as clipped controls, and sham-operated animals were normal controls. Western blot analysis was used to estimate the protein levels and ELISA for PGE2 and TXB2. Results: Levels of NHE-1 and NHE-3 protein in the unclipped kidneys of both treatment groups were increased, whereas levels of α-actin, PNP activity and crude microsomes remained unchanged. These changes were significantly reduced by long-term, and not by short-term treatment with cilazapril. In group 1 clipped kidneys, NHE-3 and α-actin proteins were increased, and crude microsomes and PNP activity were decreased. In group 2 clipped kidneys, both NHE-1 and 3 isoforms were induced, whereas PNP activity was decreased. Cilazapril did not reverse the changes in the clipped kidneys in both groups, but reduced the crude microsomes. Group 2 unclipped kidneys showed hypertrophy, which remained unaffected by cilazapril treatment. Induced levels of BP, PGE2 and TXB2 in both groups were reduced significantly except for the 24-hour post-cilazapril treatment. Conclusions: These findings demonstrate a differential expression of NHE-1 and NHE-3 isoforms which is dependent on the rise in BP, PGE2 or TXB2 in the long-term treatment group, but not in the short-term treatment group. Thus, the changes in NHE isoforms and sodium pump activity, together, contribute to functional differences that exist in the 2K-1C kidneys.

Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications.

Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM.