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Mahran, L. G., A. S. el-Khatib, A. M. Agha, and M. T. Khayyal, "The protective effect of aqueous propolis extract on isolated rat hepatocytes against carbon tetrachloride toxicity.", Drugs under experimental and clinical research, vol. 22, issue 6, pp. 309-16, 1996. Abstract

The protective effect of honeybee aqueous propolis extract (APE) against the hepatotoxicity of carbon tetrachloride was investigated using isolated liver-cell suspensions as the experimental model. Various concentrations of the extract were preincubated with the hepatocyte suspensions for 30 min before being subjected to the hepatotoxin for a further 30 min. The hepatocyte toxicity was assessed using three parameters, namely, the release of lactate dehydrogenase, the formation of lipid peroxides and the depletion of intracellular reduced glutathione. It was found that a dose-related protection against the induced cell injury was conferred by APE as evidenced by its inhibitory influence on the changes induced by CCl4 on the measured parameters. The hepatocyte protective effect of APE is probably a result of its antioxidant and free-radical-scavenging properties which in turn help to maintain the intracellular level of reduced glutathione.

Mansour, S. M., A. K. Bahgat, A. S. El-Khatib, and M. T. Khayyal, "Ginkgo biloba extract (EGb 761) normalizes hypertension in 2K, 1C hypertensive rats: role of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 18, issue 8-9, pp. 641-7, 2011 Jun 15. Abstract

The 2 kidney, 1-clip (2K, 1C) model of hypertension was used to investigate the potential antihypertensive effect of a standardized leaf extract of Ginkgo biloba (EGb 761). Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) reaching a plateau after 4 weeks of surgery. Treatment of hypertensive rats with EGb 761 (60, 90, 180 mg/kg/day orally) was therefore started 4 weeks after surgery and continued for 3 weeks. This led to a dose-dependent reduction in SBP with no significant change in heart rate. Control hypertensive rats showed a significant elevation of total protein thiols (Pr-SHs level) in both clipped and non-clipped kidneys as well as in the serum. However, glutathione peroxidase (GSH-Px) activity was decreased in the clipped kidneys but elevated in the non-clipped ones and in the blood. The malondialdehyde (MDA) level was raised in clipped kidneys but not in non-clipped ones nor in the serum. Nitric oxide (NO level) and angiotensin converting enzyme (ACE) activity were increased in both clipped and non-clipped kidneys but not in the serum. Endothelium-dependent and -independent relaxation of aortic rings towards acetylcholine (Ach) and sodium nitroprusside (SNP) were impaired. Treatment with EGb 761 (180 mg/kg/day for 3 weeks) was associated with recovery of GSH-Px activity in clipped kidneys, inhibition of ACE activity in both kidneys and a reduction in the elevated NO level of the non-clipped kidneys, decreased responsiveness to the vasoconstrictor NE and improvement of endothelial function as evidenced by restoration of endothelium-dependent vasorelaxation induced by Ach. The observed beneficial effects of the EGb 761 may be attributed to different factors, including ACE inhibition and maintenance of cellular antioxidant capacity as well as preserving vascular reactivity towards endothelium-dependent and -independent vasodilators while inhibiting responses to vasoconstrictors.

Mansour, M., A. S. el-Khatib, and O. El-Ahmady, "INHIBITED GENERATION OF LEUKOTRIENES FROM STIMULATED HUMAN LEUKOCYTES BY THE AQUEOUS EXTRACT OF PROPOLIS", Bull. Fac. Pharm. Cairo Uni, vol. 33, issue 2, pp. 75-79, 1995.
Mansour, M. A., O. T. Ginawi, T. El-Hadiyah, A. S. el-Khatib, O. A. Al-Shabanah, and H. A. Al-Sawaf, "Effects of volatile oil constituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: evidence for antioxidant effects of thymoquinone.", Research communications in molecular pathology and pharmacology, vol. 110, issue 3-4, pp. 239-51, 2001. Abstract

Effects of the volatile oil constituents of Nigella sativa, namely, thymoquinone (TQ), p-cymene and alpha-pinene, on carbon tetrachloride (CCl4-indued acute liver injury were investigated in mice. A single dose of CCl4 (15 microl/Kg i.p.) induced hepatotoxicity 24 h after administration manifested biochemically as significant elevation of the enzymes activities of serum alanine transaminase (ALT, EC:2.6.1.2), asparate transaminase (AST, EC:2.6.1.1) and lactate dehydrogenase (LDH, EC: 1.1.1.27). The toxicity was further evidenced by a significant decrease of non-protein sulfhydryl(-SH) concentration, and a significant increase of lipid peroxidation measued as malondialdhyde (MDA) in the liver tissues. Administration of different doses of the TQ (4, 8, 12.5, 25 and 50 mg/Kg i.p.) did not alter the chosen biochemical parameters measured, while higher doses of TQ were lethal. The LD50 was 90.3 mg/Kg (77.9-104.7, 95% CL). Pretreatment of mice with different doses of TQ 1 h before CCl4 injection showed that the only dose of TQ that ameliorated hepatotoxicity of CCl4 was 12.5 mg/Kg i.p. as evidenced by the significant reduction of the elevated levels of serum enzymes as well as hepatic MDA content and significant increase of the hepatic nonprotein sulfhydryl(-SH) concentration. Treatment of mice with the other volatile oil constituents, p-cymene or alpha-pinene did not induce any changes in the serum ALT measured. In addition, i.p. administration of these compounds 1 h before CCl4 injection, did not protect mice against CC4-induced hepatotoxicity. The results of the present study indicate that TQ (12.5 mg/Kg, i.p.) may play an important role as antioxidant and may efficiently act as a protective agent against chemically-induced hepatic damage. In contrast, higher doses of TQ were found to induce oxidative stress leading to hepatic injury.

Mansour, M. A., M. N. Nagi, A. S. El-Khatib, and A. M. Al-Bekairi, "Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action.", Cell biochemistry and function, vol. 20, issue 2, pp. 143-51, 2002 Jun. Abstract

The present investigation focused, firstly, on the effects of oral administration of thymoquinone (TQ) on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase activity in hepatic, cardiac and kidney tissues of normal mice. Superoxide dismutase (SOD; E.C:1.15.1.1), catalase (CAT; E.C:1.11.1.6), glutathione peroxidase (GSH-Px; E.C:1.11.1.9), glutathione-S-transferase (GST; E.C:2.5.1.18), and DT-diaphorase (E.C:1.6.99.2) enzyme activities in each tissue type were determined. Treatment of mice with the different doses of TQ (25, 50 and 100 mg kg(-1) day(-1) orally) for 5 successive days, produced significant reductions in hepatic SOD, CAT and GSH-Px activities. In addition cardiac SOD activity was markedly inhibited with the higher doses of TQ, (namely 50 and 100 mg kg(-1)). Moreover, TQ (100 mg kg(-1)) significantly reduced hepatic and cardiac lipid peroxidation as compared with the respective control group. Conversely, TQ (50,100 mg kg(-1)) and TQ (100 mg kg(-1)) enhanced cardiac and renal DT-diaphorase activity respectively. However, the selected doses of TQ neither produced any change in GST activity nor influenced reduced glutathione content in all tissues studied. TQ was tested, secondly, as a substrate for hepatic, cardiac and renal DT-diaphorase of normal mice in the presence of NADPH. Kinetic parameters for the reduction of TQ to dihydrothymoquinone (DHTQ) indicated that DT-diaphorase of different tissues can efficiently reduce TQ to DHTQ. K(m) and V(max) values revealed that hepatic DT-diaphorase exhibited the higher values, while the lower values were associated with renal DT-diaphorase. TQ and DHTQ were tested, thirdly, as specific scavengers for superoxide anion (generated biochemically) or as general scavengers for free radicals (generated photochemically). The results revealed that TQ and DHTQ acted not only as superoxide anion scavengers but also as general free radical scavengers. The IC(50) for TQ and DHTQ in biochemical and photochemical assays were in the nanomolar and micromolar range respectively. Our data may explain at least partly the reported beneficial in vivo protective effects of TQ through the combined antioxidant properties of TQ and its metabolite DHTQ.

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