HEPATOPROTECTIVE ACTIVITY OF MONASCUS PURPUREUS (RED RICE YEAST) IN DIABETIC RATS ALONE OR IN COMBINATION WITH PIOGLITAZONE: AN EFFECT MEDIATED THROUGH CYTOKINES, ANTIOXIDANTS AND LIPID BIOMARKERS

Objective: Diabetes induces many complications such as cardiovascular problems, cataracts, kidney damage and polyneuropathy. Streptozotocin (STZ) induced diabetes is considered one of the most common animal models in rats. The present study investigated the effects of Monascus purpureus (MP) alone or in combination with pioglitazone on glucose level and on liver in streptozotocin (STZ) diabetic rats.Methods: In this study were divided into five experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with Monascus purpureus (500 mg/kg B. W, oral), treated STZ-diabetic with pioglitazone (10 mg/kg B.W., oral) and treated STZ-diabetic with MP (250 mg/kg B. W, oral)+pioglitazone (10 mg/kg B.W., oral)). Treatment continued for 14 d then blood sampling was done to assess blood glucose. At the end of the study, the animals were fasted overnight, anesthetized with sodium pentobarbital (60 mg/kg i.p.), and sacrificed to collect tissues samples (liver, pancreases).Results: Throughout the experimental period, all treatments significantly (P<.05) lowered serum glucose, triglycerides, cholesterol, c-peptide and IL-6. In addition, hepatic cholesterol and triglycerides levels were also lowered. Moreover, the treated diabetic rats showed higher activity of reduced glutathione (P<.05) in the liver compared with the diabetic control rats and inhibited diabetes induced elevation in the level of malondialdehyde in liver.Conclusion: The results of this study clearly demonstrated that MP act by many ways, including anti-hyperglycemic, antioxidant effects and pancreatic β-cell protection. From these points, it seems that MP may be a useful supplement to alleviate the development of diabetes and its complications

ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

Antioxidant Potential of Spirulina platensis

The present study aimed to examine the protective role of Spirulina platensis (S. platensis) against arsenic-induced testicular oxidative damage in rats. Arsenic (in the form of NaAsO2 at a dose of 6.3 mg/kg body weight for 8 weeks) caused a significant accumulation of arsenic in testicular tissues as well as a decrease in the levels of testicular superoxide dismutase (SOD), catalase (CAT), reduced glutathione, and zinc. Moreover, it significantly decreased plasma testosterone, luteinizing hormone (LH), triiodothyronine (T3), and thyroxine (T4) levels and reduced sperm motility and sperm count. Arsenic (AS) led to a significant increase in testicular malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), nitric oxide (NO), and sperm abnormalities. S. platensis at a dose of 300 mg/kg was found to attenuate As-induced oxidative stress, testicular damage, and sperm abnormalities by its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect the testicular tissue from arsenic intoxication

Alleviation of haloperidol induced oxidative stress in rats: Effects of sucrose vs grape seed extract

Haloperidol (HP) is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. HP is known to induce oxidative stress due to increased turnover of dopamine. The aim of the present study was to investigate the effect of sucrose (1 and 5 mg/kg; p.o.) and grape seed extract (GSE; 100, 200 and 400 mg/kg; p.o.) on the oxidative stress induced in rats by HP (1 mg/kg; p.o.) in the liver and the brain tissues. Oxidative stress was induced by injection of HP for 14 consecutive days which was concurrently administered with sucrose and GSE. Liver and brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels were determined in the brain and liver. Results of the present study revealed that HP-treated rats showed elevated levels of NO in the brain and MDA in the brain and liver. HP-treated rats showed also decreased levels of NO levels in the liver and GSH in the brain and liver. Treatment of HP-treated rats with GSE reversed all the oxidative stress markers in both the brain and liver due to its potent antioxidant property. On the other hand, sucrose attenuates the levels of NO in the brain and liver and the brain levels of MDA and GSH. It can be concluded that both GSE (a potent anti-oxidant) and sucrose (as a source of energy) have beneficial impacts on the brains of HP-treated rats. However, GSE is more potent in alleviating the oxidative stress associated with HP in the liver

Grape seed extract attenuates hyperglycaemia-induced in rats by streptozotocin

The current study aimed to investigate the possible beneficial effects of grape seed extract (GSE) on some metabolic and biochemical changes associated with streptozotocin (STZ; 50 mg/kg; i.p.)-induced hyperglycaemia in male rats. Blood samples were used to determine serum levels of glucose, insulin, total cholesterol (TC) and triglycerides (TG). Some biochemical markers for oxidative stress viz., serum lipid peroxides level (measured as malondialdehyde; MDA) and total antioxidant capacity as well as serum nitric oxide (NO) level were assessed. Hyperglycaemic animals received GSE (100 and 300 mg/kg/day) orally on daily basis for 28 consecutive days and their effects were determined 24 h after the administration of the last dose. Results of the present study revealed that STZ-induced hyperglycaemia is associated with decreased serum insulin level with increased levels of TC and TG. Hyperglycaemia was also associated with increased level of serum MDA together with decreased total antioxidant capacity and level of serum NO. GSE succeeded to improve the serum glucose level in STZ-treated rats in a dose dependent manner. It also showed a restoration of the increased serum level of TC, TG and MDA and of the suppressed insulin and total antioxidant capacity as well as the decreased plasma level of NO. From our results it can be concluded that GSE has beneficial effects against the biochemical changes associated with STZ-induced hyperglycaemia. These beneficial effects might be related to the ability of GSE to improve hyperglycaemia in addition to its anti-oxidant property

Protective effects of ursodeoxycholic acid on ceftriaxone-induced hepatic injury in rats

Ceftriaxone is a broad-spectrum semisynthetic cephalosporin antibiotic that causes partial damage in the liver manifested by transient elevation in some biochemical parameters. In this study, our aim was to investigate the use of ursodeoxycholic acid (UDCA) in prevention of the hepatotoxic effect and biochemical changes induced by ceftriaxone in rats. Rats were divided into six groups (control, UDCA 20 mg/kg, ceftriaxone 180 mg/kg, UDCA + ceftriaxone 180 mg/kg, ceftriaxone 360 mg/kg, and UDCA + ceftriaxone 360 mg/kg). Ceftriaxone was injected intraperitoneally, and UDCA was given orally daily for four consecutive weeks. Then liver functions (serums AST, ALT, ALP, direct bilirubin, and total protein) were assessed. Histopathological examination was performed. Treatment of animals with ceftriaxone caused elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as total bilirubin level. These elevations in liver enzymes were decreased by combination ceftriaxone with UDCA. In addition, ceftriaxone caused a significant increase in malondialdehyde (MDA) and nitric oxide (NO) content but significant decrease in glutathione (GSH) content. Combination of UDCA and ceftriaxone resulted in a significant decrease in MDA, NO content and significantly elevated GSH content. It could be concluded that UDCA acts as an effective hepatoprotective agent against liver dysfunction caused by ceftriaxone, and this effect might be related to its antioxidant properties. Hepatic functions should be monitored, and the dose should be adjusted during ceftriaxone therapy

Protective role of antioxidants on thioacetamide-induced acute hepatic encephalopathy: Biochemical and Ultrastructural study

<p>Thioacetamide (TAA) has been used in development of animal models of acute hepatic encephalopathy (AHE). This experimental study was designed to evaluate effects of oral administration of vitamin C, vitamin E and their combination on liver and brain enzymes and their histologic and ultrastructure changes. Eighty Wistar rats were included and divided into five groups (16 each). Group 1 (control) received saline once intraperitoneally (IP) then administered orally saline and corn oil for 3 days. Group 2 [hepatotoxic (TAA)] were received TAA (300 mg/kg) once intraperitoneally (IP). Group 3 (vitamin C and TAA) received TAA (300 mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100 mg/kg) daily for 3 days. Group 4 (vitamin E and TAA) received TAA (300 mg/kg) once intraperitoneally (IP) and then administered orally vitamin E (200 mg/kg) daily for 3 days. Group 5 (vitamin C and vitamin E and TAA) received TAA (300 mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100 mg/kg) in combination with vitamin E (200 mg/kg) daily for 3 days. All rats were sacrificed 24 h after last treatment under anesthesia. Blood samples were collected and serum was obtained for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), total protein, triglyceride, cholesterol using spectrophotometer and ELISA kits. Liver and brain were extracted and tissue homogenate was used to measure malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO). Histological and ultrastructure examination were done. TAA induced significant increase of MDA and decreased in GSH and NO in both liver and brain homogenate with more liver affection, and increased in serum levels of AST, ALT, triglyceride, cholesterol and decreased in total protein. Furthermore, there is decrease in serum levels of AST, ALT, triglyceride, cholesterol and tissue levels of MDA and elevated serum total protein and tissue GSH and NO under the umbrella of vitamin C and vitamin E and their combination, although vitamin E is more efficient. These data showed protective effect of vitamins C and E, especially vitamin E against oxidative stress and hepatic and brain damage, and histological architecture of the liver in rats’ model of acute hepatic encephalopathy elicited by TAA.</p

Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NF-κβ is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κβ inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κβp65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-α, IL-1β, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics

Modulation of the pharmacological properties of meloxicam by octreotide in rats

The purpose of this study was to investigate the anti-inflammatory, analgesic, antipyretic and antiulcer properties of somatostatin analogue octreotide (10 and 100 μg/kg) and its influence on the effect of NSAID meloxicam (1 and 2 mg/kg) in rats. Carrageenan-induced rat paw oedema was used as an acute anti-inflammatory model as well as adjuvant-induced arthritis as a chronic model. Hot plate test on rats and acetic acid (0.6%) writhing test were used as acute analgesic models while the plantar test using an infrared beam directed to the paw of arthritic rats was used as a chronic analgesic model. Antipyretic effect was evaluated using Brewer’s yeast (44%) induced hyperthermia in rats while pylorus ligation was used as a model to evaluate the ulcerogenic effects. Meloxicam, octreotide and their combinations administered subcutaneously showed anti-inflammatory effects in both acute and chronic models. Only the high doses of meloxicam and octreotide showed significant analgesic effect in the hot plate test, while all doses showed significant analgesic effects in the acetic acid-induced writhing test and in the plantar test. In yeast-induced hyperthermia, only meloxicam has an antipyretic effect. Meloxicam resulted in profound gastric lesions and exerted deleterious effects on the gastric mucosa in pyloric-ligated rats. Octreotide did not cause any harmful effect on the gastric mucosa, besides; octreotide attenuated the harmful ulcerogenic effects of meloxicam when administered in combination with it. Both meloxicam and octreotide and their combination significantly decreased the malondialdehyde (MDA) content in the arthritic rats indicating their antioxidant effects

Regression of fibrosis by cilostazol in a rat model of thioacetamide-induced liver fibrosis: Up regulation of hepatic cAMP, and modulation of inflammatory, oxidative stress and apoptotic biomarkers.

In liver fibrosis, conversion of fibroblasts to profibrogenic myofibroblasts significantly drives the development of the disease. A crucial role of cyclic adenosine monophosphate (cAMP) in regulation of fibroblast function has been reported. Increase in cAMP levels has been found to decrease fibroblast proliferation, inhibit their conversion to myofibroblast, and stimulate their death. cAMP is generated by adenyl cyclase (AC), and degraded by cyclic nucleotide phosphodiesterase (PDE). In this study, the antifibrotic effect of a PDE inhibitor, cilostazol (Cilo), on a rat model of liver fibrosis induced by thioacetamide (TAA) was investigated. Four groups of rats were used; the first group received the vehicles and served as the normal control group, while liver fibrosis was induced in the other groups using (TAA, 200 mg/kg/biweekly for 8 successive weeks, ip). The last two groups were treated with Cilo (50 and 100 mg/kg/day, po, respectively). Induction of liver fibrosis in TAA-treated rats was observed as evidenced by the biochemical and histopathological findings. On the other hand, a potent antifibrotic effect was observed in the groups treated with Cilo, with preference to the higher dose. In these groups, a significant increase in the liver content of cAMP was demonstrated that was accompanied by reduction in the hepatic expression of key fibrogenic cytokines, growth factors, and inflammatory biomarkers, including interleukin-6, tumor necrosis factor-alpha, nuclear factor kappa B, and transforming growth factor-beta as compared to TAA group. Moreover, amelioration of TAA-induced oxidative stress and apoptosis in the liver has been observed. These findings reveal the antifibrotic effect of Cilo against TAA-induced liver fibrosis in rats, and suggest regulation of cAMP pathway, together with the modulation of oxidative stress, inflammation, and apoptosis as mechanistic cassette underlines this effect