INSIGHTS INTO THE ROLE OF MORUS ALBA IN REVERSING OBESITY-ASSOCIATED HEPATIC STEATOSIS AND RELATED METABOLIC DISORDER IN RATS

ABSTRACTObjective: The goal of the present study was to examine the viability of Morus alba (M. alba) ethanolic extract in repression of obesity-associatedhepatic steatosis and related metabolic disorder; dyslipidemia, hyperinsulinemia, and glycemic status.Methods: Adult female albino rats were randomly assigned into four groups, eight rats each as follows: Group (1) control group received standardrodent diet for 24 weeks. The other three groups administered high cholesterol diet for 12 weeks and served as obese group, M. alba-treated group,and simvastatin-treated group.Results: The current results showed an increment in thoracic circumference (TCX) and abdominal circumferences (AC) as well as body mass index(BMI) in obese group. In addition, dyslipidemia, hyperinsulinemia, hyperglycemia, and insulin resistance have been elucidated in obese group.Moreover, hepatic malondialdehyde (MDA), nitric oxide (NO), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubinvalues were significantly increased in obese groups versus control group. On the other hand, administration of ethanolic extract of Morus alba orsimvastatin could significantly lessen BMI and in addition to improve dyslipidemia in obese group. Glucose, insulin levels, and insulin resistance valuein serum samples demonstrated a significant reduction in obese group upon treatment with M. alba ethanolic extract or simvastatin. Furthermore,noticeable depletion in hepatic MDA, NO contents, serum ALT, AST activities, and serum bilirubin level was recorded as a result of treatment witheither ethanolic extract of M. alba or simvastatin. Histopathological examination of liver tissue showed ballooning degeneration in the hepatocytes(hepatic steatosis) associated with inflammatory cells penetration in portal zone in obese group. Meanwhile, the treatment of obese groups withethanolic extract of M. alba or simvastatin was found to restore the structural organization of the liver.Conclusion: The present findings provide a novel aspect for understanding of the role of M. alba against obesity-associated liver diseases and relatedmetabolic disorder. The mechanisms underlying these effects seem to depend on the hypolipidemic potential, anti-inflammatory property, andantioxidant activity of its phytochemicals.Keywords: Obesity, Morus alba, Dyslipidemia, Hyperinsulinemia, Hyperglycemia, Hepatic steatosis

QUERCETIN MITIGATES TOXICITY AND OXIDATIVE STRESS MOTIVATED BY BISPHENOL A IN LIVER OF MALE RATS

Objective: Epidemiological reports have indicated a correlation between the increasing of bisphenol A (BPA) levels in the environment and the incidence of hepatotoxicity. The present study aimed to evaluate the protective effect of quercetin on oxidative stress, inflammatory markers, apoptotic and antiapoptotic markers in the liver tissue of the bisphenol A treated rats.Methods: Forty-eight male Wistar rats were divided into six groups; Group(1): Negative control group (Con), Group(2): Corn oil control group orally administered 1 ml of corn oil/rat daily for two months (Corn), Group(3): Olive oil control group orally administered 1 ml olive oil/rat daily for two months (Olive), Group(4): Quercetin (Qu) control group orally received Qu dissolved in olive oil (50 mg/kg b. wt.) daily for two months (Qu). Group(5): Positive control group orally received Bisphenol A (BPA) dissolved in corn oil in a dose of 50 mg/kg b. wt. daily for two months (BPA), Group(6): Quercetin treated group orally administered 50 mg/kg b. wt. of BPA and treated with Qu (50 mg/kg b. wt. Orally) daily for two months (BPA+Qu).Results: BPA exposure resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde level and glutathione-S-transferase activity associated with significant decrease in glutathione peroxidase activity in the liver tissue. Moreover, BPA caused an up regulation in the values of liver function enzymes. Also, BPA produced a significant elevation in the hepatic Interleuckin-6 (IL-6) and caspase-3 levels with a significant decline in antiapoptotic protein B-cell lymphoma 2 (Bcl2) level in liver tissue. Quercetin significantly attenuated the BPA-evoked liver oxidative stress and modulated the activities of liver function enzymes. In addition, treatment of quercetin with BPA resulted in an improvement of IL-6 and caspase-3 levels associated with a significant increase in hepatic protein Bcl2 expression.Conclusion: These data suggest that quercetin protects rat liver from BPA-induced oxidative stress, probably via its antioxidant activity, anti-inflammatory and antiapoptotic effects. So, Quercetin is a promising pharmacological agent for preventing the potential hepatotoxicity of BPA following occupational or environmental exposures.Keywords: Bisphenol A, Quercetin, hepatotoxicity, Antioxidant, Anti-inflammatory effect, Antiapoptotic effec

The THE ROLE OF PLATELET RICH PLASMA AND QUERCETIN IN ALLEVIATING DIMETHYLNITROSAMINE-INDUCED ACUTE SPLEEN INJURY THROUGH REGULATING OXIDATIVE STRESS, INFLAMMATION AND APOPTOSIS

Objective: Excessive oxidative stress is implicated in spleen injury. Platelet-rich plasma (PRP) and quercetin (QUR) have been shown to protect cells against oxidative stress. This study was designed to investigate their effect on dimethyl nitrosamine (DMN) induced spleen injury in male rats. Methods: Forty male Wistar rats were divided into four groups; Group (1): Negative control group (Con), Group (2): DMN group, DMN was given intraperitonealy at a dose of 4 mg/kg b. wt/day for four weeks for sub-chronic injury of spleen tissue, Group (3): DMN+PRP, rats were injected intraperitonealy with DMN at a dose of 4 mg/kg b. wt/day for four weeks then treated i. v. by single dose 50 μL of PRP, then left for a period of four weeks without any treatments, Group(4): DMN+QUR, rats received intraperitonealy DMN at a dose of 4 mg/kg b. wt/day for four weeks, then treated with quercetin orally at a dose of 50 mg/kg b. wt. in aqueous suspension daily using an intragastric tube for four weeks. Results: DMN inoculation resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde, hydrogen peroxide and xanthine oxidase levels associated with a significant decrease in Superoxide dismutase and catalase activities in the spleen tissue as compared to the normal control group. Moreover, DMN caused an up-regulation in the values of the splenic C-reactive protein (CRP), interleuckin-6 (IL-6), nuclear factor kappa B (NF-κB), leukotriene-C4 (LT-C4), P53 and Fas levels with a significant decline in anti-apoptotic protein B-cell lymphoma 2 level as compared to the normal control group. PRP and QUR significantly attenuated the DMN-evoked spleen oxidative stress and modulated the activities of antioxidant enzymes as compared to DMN group. In addition, treatment of DMN group with PRP or QUR resulted in an improvement in CRP, IL-6, NF-κB, LT-C4, P53 and Fas levels as compared to DMN group. Caspase-3 expression was positive in DMN group while no difference was present in control, PRP and Quercetin groups. However, the VEGF immunopositive reaction was found in DMN, PRP and Quercetin groups compared to control group. Histopathological results showed degeneration, haemorrhage, inflammatory cells and necrotoic areas in splenic tissue from DMN group compared to the treated groups where signs of recovery were observed in the whole splenic tissue. Conclusion: These data suggest that PRP and QUR protect rat spleen from DMN-induced oxidative stress, probably via their antioxidant activity, anti-inflammatory and anti-apoptotic effects. So, PRP and QUR are promising pharmacological agents for preventing the potential spleen injury of DMN following occupational or environmental exposures

Two Stability Indicating Chromatographic Methods: TLC Densitometric versus HPLC Method for the Simultaneous Determination of Brinzolamide and Timolol Maleate in Ophthalmic Formulation in the Presence of Probable Carcinogenic Oxidative Degradation Product of Timolol Maleate

A comparative study between two stability-indicating chromatographic methods for the assay of brinzolamide and timolol maleate in the co-existence of the probable carcinogenic oxidative degradation product of timolol maleate in their ophthalmic formulation was demonstrated. The first method established the thin-layer chromatography coupled with the densitometric determination of the analyzed spots, using silica gel TLC aluminum plates F254 and a developing system of chloroform: methanol: ammonia (6:1:0.1, in volumes) at room temperature to give good separation for the three investigated components, where retardation factors for the oxidative degradation product of timolol maleate, brinzolamide and timolol maleate were (Rf 0.21), (Rf 0.46), and (Rf 0.55), respectively. The linear ranges were 2–10 and 3–16 μg/band for brinzolamide and timolol maleate, respectively. In the second method, high performance liquid chromatography (HPLC), photo diode array detection was used on a Eurospher 5 µm C18 100 Å (4.6 × 250 mm) column, using triethylamine pH 3.5, adjusted by glacial acetic acid: acetonitrile (20:80, v/v) at a rate of 0.5 mL per minute. An acceptable separation was achieved, where the retention times for timolol maleate, the oxidative degradation product of timolol maleate and brinzolamide, were (Rt 3.6), (Rt 4.7), and (Rt 5.6), respectively. Linearity covered a range of 20–120 μg/mL for both drugs. It has been proved previously that timolol maleate is liable to oxidation, giving a high-probability carcinogenic product in female mice. The validation for the new proposed stability-indicating methods was optimized in line with the ICH guidelines with good outcomes. It is worth noting that the HPLC-DAD method showed superior separation, economic and time-saving results, while TLC method was more sensitive

PERSPECTIVE IN THE TREATMENT OF ALZHEIMER'S DISEASE: PRE-CLINICAL STUDY

Objective: This study end to investigate the efficacy of α-chymotrypcin in management of Alzheimer's disease (AD) in the experimental model. Methods: Sixty adult female albino rats were divided into four groups, (1) normal control group, (2) rats underwent surgery to remove ovaries (Ovex group), (3) Ovx rats received aluminum chloride to induced AD (AD group) and (4) AD rats treated with α-chymotrypcin (α-ch group). Results: In comparison with the normal control group, the Ovx group recorded significant increase in the brain level of transforming growth factor-β, while the brain levels of brain derived neurotrophic factor and vascular endothelial growth factor were significantly decreased. Similarly, AD group displayed the same effect versus the Ovex  group. Treatment of AD group with α-chymotrypcin resulted in significant improvement in the biochemical parameters as compared to untreated AD group. These results were confirmed by the histological examination of brain tissue. Conclusion: The current study suggests that α-chymotrypcin has a potent role in restraining AD due to its proteolytic and anti-inflammatory activity