Muhammad Dawood Shah

Diazinon-induced oxidative stress and renal dysfunction in rats

Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.

In vitro total phenolics, flavonoids contents and antioxidant activity of essential oil, various organic extracts from the leaves of tropical medicinal plant Tetrastigma from Sabah

OBJECTIVE To detect the in vitro total phenolics, flavonoids contents and antioxidant activity of essential oil, various organic extracts from the leaves of tropical medicinal plant Tetrastigma from Sabah. METHODS The dry powder leaves of Tetrastigma were extracted with different organic solvent such as hexane, ethyl acetate, chloroform, butanol and aqueous methanol. The total phenolic and total flavonoids contents of the essential oil and various organic extracts such as hexane, ethyl acetate, chloroform, butanol and aqueous ethanol were determined by Folin - Ciocalteu method and the assayed antioxidant activity was determined in vitro models such as antioxidant capacity by radical scavenging activity using α, α-diphenyl- β-picrylhydrazyl (DPPH) method. RESULTS The total phenolic contents of the essential oil and different extracts as gallic acid equivalents were found to be highest in methanol extract (386.22 mg/g) followed by ethyl acetate (190.89 mg/g), chloroform (175.89 mg/g), hexane (173.44 mg/g), and butanol extract (131.72 mg/g) and the phenolic contents not detected in essential oil. The antioxidant capacity of the essential oil and different extracts as ascorbic acid standard was in the order of methanol extract > ethyl acetate extract >chloroform> butanol > hexane extract also the antioxidant activity was not detected in essential oil. CONCLUSIONS The findings show that the extent of antioxidant activity of the essential oil and all extracts are in accordance with the amount of phenolics present in that extract. Leaves of Tetrastigma being rich in phenolics may provide a good source of antioxidant.

Gas chromatography-mass spectrometry analysis of various organic extracts of Merremia borneensis from Sabah

OBJECTIVE To analyse the chemical composition of different extracts of Merremia borneensis (M. borneensis) by gas chromatography-mass spectrometry (GC-MS). METHODS The dried leaves powder was extracted with methanol at room temperature by using Soxhlet extractor. Methanol crude extracts of M. borneensis were extrastel with hexane, chloroform, ethyl acetate and butanol. RESULTS Qualitative analyses of various organic crude extracts showed that majority of these are flavonoids, terpeniods, alkaloids and glycosides. Most of the identified compounds by GC-MS are biologically important. Further the M. borneensis leaf possesses certain characteristics that can be ascribed to cultivation on a domestic plantation. CONCLUSIONS The suitable extracts for respective compounds can be chosen on the basis of above GC-MS analysis. All the major compounds from different extracts are biologically active molecules. Thus the identification of a good number of compounds from various extracts M. borneensis might have some ecological significance.

Antioxidative and chemopreventive effects of Nephrolepis biserrata against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic dysfunction in rats.

Abstract Context: Nephrolepis biserrata L. (Nephrolepidaceae) has been used in folk medicine for protection against different diseases. Objective: The current research investigated the protective effect of the methanol extract of N. biserrata leaves against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Materials and methods: Total phenolic content and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were estimated. In addition, Sprague–Dawley (SD) rats were randomly divided into six groups: control, CCl4 (1.0 mg/kg b wt), N. biserrata extract (at doses of 125, 250, and 375 mg/kg b wt) with CCl4 and N. biserrata extract (at dose of 375 mg/kg b wt) alone. After 2 weeks all rats were sacrificed and hepatoprotective effect of N. biserrata was evaluated. Results: Our results indicated that the high total phenolic content (127.28 ± 1.57 mg GAE/g) of N. biserrata may be the major contributor to strong antioxidant activities. Moreover, N. biserrata significantly depleted the elevation of enzymatic levels of alanine aminotransferase and aspartate aminotransferase (20–93% recovery), reduced the extent of malondialdehyde (47–90% recovery), increased the level of reduced glutathione (25–39% recovery), and elevated the activities of catalase, glutathione reductase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione S-transferase, and quinone reductase (5–34% recovery). Histopathological observations also revealed that N. biserrata decreased fatty degeneration and necrosis in CCl4 administered rats. Discussion and conclusion: N. biserrata has strong antioxidant activities and significant protective effects against CCl4 induced hepatotoxicity in rats.

Hepatoprotective and Immunosuppressive Effect of Synedrella nodiflora L. on Carbon Tetrachloride (CCl4)-Intoxicated Rats.

Synedrella nodiflora is a medicinal plant that is used by the natives of Sabah, Malaysia to treat rheumatism and several other ailments. This study aims to evaluate the ability of the crude aqueous extract of S. nodiflora leaves to protect against carbon tetrachloride (CCl4)-mediated hepatic injury in rats. S. nodiflora aqueous extract was orally administered to adult Sprague Dawley rats once daily for 14 days (150 and 300 mg/kg body weight [b.w.]) before CCl4 oral treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), hepatic antioxidant enzymes, and malondialdehyde (MDA) levels were estimated. Immunohistochemistry was performed for oxidative stress markers (4-hydroxynonenal [HNE], 8-hydroxy-deoxyguanosine [8-OHdG]) and proinflammatory markers (tumor necrosis factor-α, interleukin-6, prostaglandin E2). Biochemical, immunohistochemical, histological, and ultrastructural findings were in agreement to support the hepatoprotective effect of S. nodiflora against CCl4-mediated oxidative hepatic damage. Hepatoprotective effects of S. nodiflora might be attributable to the presence of phenolic antioxidants and their free radical scavenging property.

Hepatoprotective mechanism of Lygodium microphyllum (Cav.) R.Br. through ultrastructural signaling prevention against carbon tetrachloride (CCl4)-mediated oxidative stress

Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.

Chemical composition and antioxidant activity of essential oil of leaves and flowers of Alternanthera sessilis red from Sabah

Article history: Received on: 11/04/2016 Revised on: 19/05/2016 Accepted on: 07/07/2016 Available online: 28/12/2016 In the present study, chemical composition and antioxidant activity of essential oil from the aerial parts of Alternanthera sessilis red has been investigated. The chemical composition of essential oil of A. sessilis red was determined by GC-MS analysis. Determination of antioxidant nature of A. sessilis red was carried out by 1,1diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method using butylated hydroxytoulene (BHT)as the positive control. The major components of essential oil of leaves, as analyzed by the GC-MS were found to be 1,1,1,5,5,5-hexamethyl-3,3-bis[trimethylsilyl)oxy]trisiloxane (15.43%), S,S-dioxide trans-2-methyl-4-Npentylthiane (11.27%), didodecylphthalate (10.62%) and tetrahydro-2,5-dimethoxy furan (10.01%).However, the major components of essential oil of flower were 1,1,1,5,5,5-hexamethyl-3,3bis[trimethylsilyl)oxy]trisiloxane (17.76%), trans-4-ethyl-5-octyl-2,2-bis(trifluromethyl)-1,3-dioxolane (11.12%) and tetrahydro-2,5-dimethoxy furan ( 9.10%).