Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells.

Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.

Monitoring metal levels in water and multiple biomarkers in the grouper ( Epinephelus tauvina) to assess environmental stressors on the Arabian Gulf coast of Saudi Arabia.

In this field study, the levels of heavy metals (Pb, Fe, Co, Cu, and Zn) in water and a suite of biochemical and histological biomarkers in the grouper ( Epinephelus tauvina) were assessed at four sites in the Arabian Gulf. Samples were taken from a relatively non-urban reference site, called Salwa (S1), and three effluent-dominated sites, namely Al-aziziyah in southern Dammam city (S2), the Al-Jubail coast (S3), and Manifa (S4). Toxic metals, namely Pb and Co (at all sites) and Fe (at S3), were elevated in water samples relative to the internationally permissible limits. In fish, induced levels of heat shock protein 70 (HSP70) in the liver at S3 and S4 were higher than those of the reference fish at S1. Additionally, the level of the lipid peroxidation (LPO) product (malondialdehyde (MDA)) was significantly increased in gills (at S3) and liver (at S2 and S3). There was an inhibition of catalase activities in the gills of fish from S2 to S4 and significantly higher activity levels of superoxide dismutase in the gills of fish from S4. Histopathological features such as aneurysms in gill vessels, deformed gill lamellae, increases in liver melano-macrophage centers, and hepatocellular necrosis were most abundant at sites where significant pollution problems exist (i.e. S2-S4). The results reveal that the eastern coast of Saudi Arabia, in the Arabian Gulf, is still contaminated, as indicated by elevated HSP70, LPO content and numbers of histological lesions, and that monitoring of contaminants and their effects should be continued in this region.

Spinosad Induces Antioxidative Response and Ultrastructure Changes in Males of Red Palm Weevil Rhynchophorus ferrugineus (Coleoptera: Dryophthoridae).

The red palm weevil, Rhynchophorus ferrugineus, is of great concern worldwide, especially in the Middle East, where dates are a strategic crop. Despite their ecological hazard, insecticides remain the most effective means of control. A bioinsecticide of bacterial origin, spinosad is effective against several pests, and its efficacy against male R. ferrugineus was assessed in the present study. The antioxidative responses of key enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) to spinosad were investigated in the midgut and testes, and the effects of this insecticide on the cell ultrastructure of the midgut, Malpighian tubules, and testes were also determined. The lethal concentration 50 of spinosad was measured at 58.8 ppm, and the insecticide inhibited the activities of CAT, SOD, and GST in the midgut. However, no significant changes in the activities of these enzymes were observed in the testes. Spinosad treatment resulted in concentration-dependent changes in the cellular organelles of the midgut, Malpighian tubules, and testes of R. ferrugineus, and some of these effects were similar to those exerted by other xenobiotics. However, specific changes were observed as a result of spinosad treatment, including an increase in the number and size of concretions in Malpighian tubule cells and the occasional absence of the central pair of microtubules in the axonemes of sperm tails. This study introduces spinosad for potential use as an insecticide within an integrated control program against male red palm weevils. Additionally, the study provides biochemical and ultrastructural evidence for use in the development of bioindicators.

Hemin attenuates cisplatin-induced acute renal injury in male rats.

BACKGROUND: The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. METHODS: The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. RESULTS: A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. CONCLUSION: The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.

Histopathological biomarkers in gills and liver of Oreochromis niloticus from polluted wetland environments, Saudi Arabia.

Fish live in direct contact with their immediate external environment and, therefore, are highly vulnerable to aquatic pollutants. In this study, Oreochromis niloticus were caught at three different sites in Al-Hassa irrigation channels, namely Al-Jawhariya, Um-Sabah and Al-Khadoud. The histological changes in gills and liver were detected microscopically and evaluated with semi-quantitative analyses. Also, heavy metals have been determined in the water samples in these sites. Results showed that all sites were polluted by different kinds of heavy metals. Cd and Pb were mostly detected at concentrations above the WHO reference values. Meanwhile, various histopathological abnormalities were observed in gills and liver of fish specimens. In the gill filaments, cell proliferation, lamellar cell hyperplasia, lamellar fusion, lifting of the respiratory epithelium, and the presence of aneurysmal areas were observed. In the liver, there was vacuolization of the hepatocytes, sinusoidal congestion, necrosis of the parenchyma tissue, nuclear pyknosis, eosinophilic hepatocellular degeneration, pigment accumulation, an increase in the number and size of melanomacrophage centers. Liver tumors with severe chronic inflammation were occasionally found in fish at Al-Khadoud area (first-time report). The histological lesions were comparatively most severe in the liver. Despite heavy metals assessment did not show marked differences among sites, histopathological biomarkers indicated that the surveyed fish are living under stressful environmental conditions. So, we suggest use those biomarkers in future monitoring of aquatic systems.