trans-Anethole attenuated renal injury and reduced expressions of angiotensin II receptor (AT1R) and TGF-ß in streptozotocin-induced diabetic rats.

Fibrosis is a pathological process in diabetic nephropathy that causes renal failure and dysfunction. Given the known anti-diabetic effects of trans-Anethole (TA), we aimed to investigate its renoprotective and anti-fibrotic effect alone and in combination with losartan in diabetic nephropathy. Male Wistar rats received a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ) for diabetes induction. Diabetic rats were treated orally with saline, TA (80 mg/kg), losartan (Los; 10 mg/kg), or the combination of TA and losartan (TA-Los) daily for five weeks. Renal function was monitored during the study, and renal fibrosis, oxidative stress markers, apoptotic cells, and the expression and localization of AT1R, TGF-ß1, and Col-IV were detected in the kidney. Results showed that TA alone and in combination with losartan was able to decrease blood glucose, urea, and creatinine levels and improve kidney function parameters. TA, Los, and TA-Los significantly reduced tubule vascular degeneration, glomerular and tubulointerstitial sclerosis, oxidative stress, and apoptotic cells. Immunohistochemistry analyses showed that TA, losartan, and TA-losartan combination downregulated the AT1R, Col IV, and TGF-ß1 expression and distribution in diabetic rat kidneys. Results suggest that TA is able to suppress diabetic nephropathy in rats effectively, probably by decreasing blood glucose levels and downregulating AT1R and TGF-ß1 expression.

Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats.

Aim: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It is also commonly used to induce hypothyroidism in rodents. PTU administration and hypothyroidism have been shown to affect the liver function. Nigella sativa (NS) has been suggested to have antioxidant and hepatoprotective effects. The objective of this study was to investigate the effects of NS extract administration during neonatal and juvenile growth period on liver function of PTU-induced hypothyroid rats.Methods: The pregnant rats were kept in separate cages. After delivery, the mothers and their offspring were randomly divided into five groups and were treated with the following programs: (1) control; (2) PTU, 0.005% in their drinking water (3-5); PTU-plus 100, 200, or 400 mg/kg NS extract. After lactation period, the offspring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten offspring of each group were randomly selected and weighted at days 10, 30, and 60 after delivery. Their blood samples were collected and the liver tissues were removed.Results: Malondialdehyde (MDA) concentration was increased while, thiol concentration and superoxide dismutase (SOD) and catalase (CAT) activity were decreased in the liver tissues of PTU-treated rats. Serum aspartate amino transferase (AST), alkaline phosphatase (ALK-P), and alanine aminotransferase (ALT) levels in the PTU group were higher than the control group. Treatment with 200 and 400 mg/kg decreased MDA while increasing thiol concentration in the liver tissues compared to the PTU group. Treatment with all doses of the extract decreased serum ALK-P concentration compared with the PTU group. Treatment with 400 mg/kg NS increased CAT and SOD concentrations in the liver tissues and decreased serum AST and ALT concentrations compared to the PTU group. PTU decreased body weight gain of offspring and while, the extract increased the body weight gain of offspring rats.Conclusion: The results of this study demonstrated that administration of NS hydroalcoholic extract in the neonatal and juvenile growth period has an improving effect on the liver function of PTU- induced hypothyroid rats.

The effects of vitamin C on hypothyroidism-associated learning and memory impairment in juvenile rats.

In this study the effects of Vitamin C (Vit C) on hypothyroidism-associated learning and memory impairment in juvenile rats was investigated. The pregnant rats were kept in separate cages. After delivery, they were randomly divided into six groups and treated: (1) Control; (2) Propylthiouracil (PTU) which 0.005% PTU in their drinking; (3-5) Propylthiouracil- Vit C groups; besides PTU, dams in these groups received 10, 100 and 500 mg/kg Vit C respectively, (6) one group as a positive control; the intact rats received an effective dose, 100 mg/kg Vit. C. After delivery, the pups were continued to receive the experimental treatments in their drinking water up to 56th day of their life. Ten male offspring of each group were randomly selected and tested in the Morris water maze (MWM) and passive avoidance (PA) which were started at 63th day (one week after stopping of the treatments). Brains were then removed for biochemical measurements. PTU increased time latency and traveled distance during 5 days in MWM while, reduced the spent time in target quadrant in MWM and step-trough latency (STL) in PA. PTU decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) activities in the brain while, increased molondialdehyde (MDA). In MWM test, 10, 100 and 500 mg/kg Vit C reduced time latency and traveled distance without affecting the traveling speed during 5 days. All doses of Vit C increased the spent time in target quadrant in probe trail of MWM and also increased STL in PA test. Vit C increased thiol, SOD and CAT in the brain tissues while, reduced MDA. Results of present study confirmed the beneficial effects of Vit C on learning and memory. It also demonstrated that Vit C has protective effects on hypothyroidism-associated learning and memory impairment in juvenile rats which might be elucidated by the antioxidative effects.

The prevention and treatment effects of egg yolk high density lipoprotein on the formation of atherosclerosis plaque in rabbits.

OBJECTIVES: Atherosclerosis is the main leading cause of cardiovascular diseases. The purpose of this study was to assess the potential preventive effect of egg yolk HDL on the atherosclerosis plaque formation. MATERIALS AND METHODS: Thirty rabbits were divided into five groups: A; normal diet, B; hyper-cholesterolemic diet, C; hypercholesterolemic + 400 mg/kg egg yolk HDL D; hypercholesterolemic +100 mg/kg egg yolk HDL and E; 200 mg/kg egg yolk HDL. At the end of the experiment, the lipid profiles were measured by spectrophotometric method. The histological sections of thoracic aorta also were taken and analyzed under light microscope. RESULTS: At the end of the 2(nd) and the 4(th) weeks, there was a significant increase of cholesterol level in groups B, C, and D compared to group A (P<0.05). Following HDL treatment, triglyceride (TG) levels increased significantly versus group A and also the TG level decreased significantly in group C, D, and E versus group B (P<0.01). Egg yolk HDL significantly increased HDL-C in groups C, D, and E (P<0.01) compared to groups A and B (P<0.05). The surface area of the atherosclerotic plaque was increased significantly in group B versus group A (P<0.001). Egg yolk HDL consumption reduced the plaque size significantly (P<0.001). CONCLUSION: Our findings indicated that treatment with egg yolk HDL increased serum HDL-C and decreased atherosclerotic plaque size in rabbits. Thus, egg yolk HDL may be considered as an anti-atherosclerotic treatment for cardiovascular diseases.

The effects of soy extract on spatial learning and memory damage induced by global ischemia in ovariectomised rats.

BACKGROUND: The effects of soy extract on memory as well as the oxidative damage to brain tissue induced by ischemia was investigated in ovariectomised (OVX) rats. METHODS: THE RATS WERE DIVIDED INTO: 1) Sham; 2) OVX; 3) Sham­Ischemia; 4) OVX­Ischemia; 5) OVX-Ischemia-S 20; and 6) OVX-Ischemia-S 60. The common carotid artery was occluded (30 minutes), and it was then re-perfused. The OVX-Ischemia-S 20 and OVX-Ischemia-S 60 groups received 20 or 60 mg/kg of soy extract for eight weeks before the ischemia. RESULTS: The Sham-Ischemia and OVX-Ischemia groups took a longer time to reach the platform while, spent a shorter time in the target quadrant (Q1) than the Sham and OVX. The escape latencies in the OVX-Ischemia-S 20 and OVX-Ischemia-S 60 groups were lower while, time spent in the Q1 was higher than that of the OVX-Ischemia. In the rotarod test, there were no significant differences between the groups. The hippocampal concentrations of malondialdehyde (MDA) in the Sham-Ischemia and OVX-Ischemia groups were higher than the Sham and OVX. Pre-treatment by 20 and 60 mg/kg of the extract reduced the MDA. CONCLUSION: It is suggested that soy prevents memory impairment and brain tissue oxidative damage due to ischemia in OVX rats.

The Effects of Aqueous Extract of Alpinia Galangal on Gastric Cancer Cells (AGS) and L929 Cells in Vitro.

BACKGROUND: Although the incidence of gastric cancer is declining during the last half century, this cancer still is the second morbid cancer in the world after lung cancer. The incidence of gastric cancer is 26 per 100,000 in Iran. This study evaluated the effect of Alpinia galangal on AGS cells (human gastric adenocarcinoma epithelial cell line) and L929 cells (as a standard cell line originated from mouse fibroblast cells). METHODS: After culturing the cells in Roswell Park Memorial Institute (RPMI) medium, the cells were incubated with different doses of Alpinia galangal (0 (control), 125, 250, 500, 750 and 1000 µg/ml) in 24, 48 and 72 hour periods and then, cells viability were assessed using MTT based cell proliferation assay. RESULTS: After 24 hours, the percentage of living AGS cells compared to the control group showed no significant decrease at the concentrations of 125 and 250µg/ml. But in the rest concentrations were significant (p<0.05). Only, the percentage of surviving L929 cells at concentration of 125µg/ml of the extract was not significant, but these percentages in the other concentrations were significant. After 48 and 72h incubation, in the last three extract concentrations, the percentage of living AGS and L929 cells significantly decreased compared to control cells (p<0.05). CONCLUSION: We have demonstrated, using cell culture model, anti-proliferative effect of aqueous extract of Alpinia galangal on human gastric tumor (AGS) and L929 cell lines. This effect was prominent in high concentrations.

Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide.

BACKGROUND: The contribution of neuroinflammation in Alzheimer's disease (AD) has been widely reported. The effects of female gonadal hormones in both neuroinflammation and brain cognitive functions have also been well considered. OBJECTIVES: In the present study, the possible protective role for endogenous ovarian hormones against learning and memory impairment as well as brain tissues oxidative damage induced by lipopolysachride (LPS) was investigated in rats. MATERIALS AND METHODS: THE RATS WERE DIVIDED INTO FOUR GROUPS: Sham-LPS, Ovariectomized (OVX)-LPS, Sham, and OVX. The animals of sham group were in proestrous phase in which the serum concentration of estradiol is high. The Sham-LPS and OVX-LPS groups were treated with LPS (250 µg/kg) before acquisition. The animals were examined using passive avoidance (PA) test. The brains were then removed and malondialdehyde (MDA) and total thiol groups concentrations were measured. RESULTS: The time latency to enter the dark compartment by OVX-LPS group was shorter than that of OVX at both first and 24th hours after the shock (P < 0.05 - P < 0.001). In Sham-LPS and OVX-LPS groups, total thiol concentration in hippocampal and cortical tissues were significantly lower while MDA concentrations were higher than that of Sham and OVX groups (P < 0.05 - P < 0.001). ). The hippocampal MDA concentration in OVX-LPS group was higher than Sham- LPS group (P < 0.01). CONCLUSIONS: Brain tissue oxidative damage contributed in deleterious effects of LPS on learning and memory. Some protective effects for the endogenous ovarian hormones against damaging effects of LPS on learning and memory function, as well as brain tissues oxidative damage could be postulated; however, it needs more investigation.

Antihyperglycemic and antihyperlipidemic effects of guar gum on streptozotocin-induced diabetes in male rats.

BACKGROUND: Herbal medicine is widely used in the treatment of diseases like diabetes mellitus. We investigated the effects of guar gum in diabetic rats for the reduction of the risk of diabetes and cardiovascular disease. Dietary pattern emphasizing foods high in complex carbohydrates and fiber are associated with low blood glucose and cholesterol levels. MATERIALS AND METHODS: Diet containing 0%, 5%, 10% and 20% (w/w) guar gum was fed to diabetic rats for 28 days. Blood serum glucose, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol levels, atherogenic index levels, body weights and food intake were monitored at 0, 7.14 and 28 days after induction of diabetes. RESULTS: In spite of the fact that diabetes elevated blood lipids in all rats after 14 days, the guar gum diet significantly decreased the serum concentration of cholesterol, triacylglicerols and LDL-C and atherogenic index. The most significant result in this study was the reduction of blood glucose in diabetic rats treated with the guar gum diet after 28 days versus non- and glibenclamide-treated rats. The gum promoted a general improvement in the condition of the diabetic rats in body weight and food intake in comparison with nontreated rats. CONCLUSION: The results of this research suggest that guar gum was significantly effective in comparison with glibenclamide in the treatment of hyperlipidemia and hyperglycemia in diabetes rats. Therefore, it may be suggested as a reliable fiber in diabetic regimes in diabetic patients.

Different responses of nitric oxide synthase inhibition on morphine-induced antinociception in male and female rats.

The roles of gonadal hormones and nitric oxide on pain perception and their interaction have been widely investigated. In the present study the chronic effect of l-NAME (NOS inhibitor) on morphine-induced antinociception in male and female rats was investigated. Forty rats were divided into four groups: (1) female (2) female-LN (3) male (4) and male-LN. The animals of groups 2 and 4 received daily injection of l-NAME (10mg/kg) during 3 weeks. The animals of control groups 1 and 3 received 2ml/kg saline instead of l-NAME. Finally, all animals were tested on the hot plate test (52±0.2°C; Cut-off 80s) to evaluate the antinociceptive effects of morphine. The hot plate test was performed for base record 15min before the injection of morphine (10mg/kg; s.c.) and consequently it was repeated every 15min after the injection. There were no significant differences in baseline latencies among all groups. Reaction times after injection of morphine in female-LN were higher than in the female control group (p<0.01). There was, however, no significant difference between male control and male-LN groups. Reaction times in the female-LN group were significantly higher than in the male-LN group. Reaction times after injection of morphine in the male group was longer than in the female group (p<0.01). It is concluded that sex hormones such as testosterone and estrogen have a role in pain perception and analgesia. NO has a modulatory effects on functions of sex hormones in pain perception and analgesic effects of opioids.

The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.

Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth.

INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05). CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated.

Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03 percent methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05). CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated.