Immunomodulatory effects of Premna tomentosa (L. Verbenaceae) extract in J 779 macrophage cell cultures under chromate (VI)-induced immunosuppression

OBJECTIVE: In the present study, the immunomodulatory effects of Premna tomentosa extract against chromate (VI)-induced toxicity was assessed in J 779 macrophage cell line. DESIGN: The cells were analyzed for cytotoxicity, phagocytosis, oxidant burst, antioxidant status, and cell proliferation. RESULT: Chromate treatment resulted in a significant increase in cytotoxicity and free radical production. Furthermore, there is a significant decrease in reduced glutathione (GSH) levels and glutathione peroxidase activity (GPx). There was an appreciable decrease in cell proliferation and phagocytosis by macrophages in the presence of chromate. However, pretreatment of the cells with P. tomentosa extract (500 microg concentration), 30 minutes prior to chromate (VI) treatment resulted in a significant inhibition of chromate-induced cytotoxicity and reactive oxygen species production. The extract also restored the antioxidant status, cell proliferation, and phagocytosis similar to that of control cells. CONCLUSION: The results confirm the cytoprotective and immunomodulatory effects of the leaves of P. tomentosa and its possible usage in immunosuppressed conditions.     

Persistent sciatic artery aneurysm with limb-threatening ischemia

A 50 year old lady with bilateral persistent sciatic artery aneurysm presented with severe limb ischemia due to distal embolization from a thrombus filled persistent sciatic artery aneurysm on one side. Persistent sciatic artery is a rare embryological anomaly which results due to the failure of development of the femoral system. Its complete variant can be clinically recognised by the presence of a weak femoral pulse with a normal popliteal pulse. The diagnostic and treatment considerations of this rare anomaly are described.     

Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular carcinoma

Dysregulated cell proliferation and tumorigenesis is frequently encountered in several cancers including hepatocellular carcinogenesis (HCC). Thus, agents that inhibit cell proliferation and restrain hepatic tumorigenesis through cell cycle regulation have a beneficial effect in the treatment of hepatocellular carcinogenesis. The present study was aimed to investigate the efficacy of thymoquinone (TQ), an active compound derived from the medicinal plant Nigella sativa, on N-nitrosodiethylamine (NDEA) [0.01% in drinking water for 16 weeks]-induced hepatocarcinogenesis in experimental rats. After experimental period, the hepatic nodules, liver injury markers and tumor markers levels were substantially increased in NDEA induced liver tumors in rats. However, TQ (20 mg/kg body weight) treatment greatly reduced liver injury markers and decreased tumor markers and prevented hepatic nodule formation and reduced tumor multiplicity in NDEA induced hepatic cancer bearing rats and this was evident from argyrophilic nucleolar organizer region (AgNORs) staining. Moreover, the uncontrolled cell proliferation was assessed by specific cell proliferative markers [proliferating cell nuclear antigen (PCNA) and Ki67] by immunofluorescence, immunoblot and analysis of mRNA expression. Simultaneously, we assessed the activity of TQ on G1/S phase cell cycle regulation with specific cell cycle proteins (p21^WAF1/CIP1, CDK4, Cyclin D1 and Cyclin E) by immunoprecipitation in experimental rats. Treatment with TQ significantly reduced the detrimental alterations by abrogating cell proliferation, which strongly induced G1/S arrest in cell cycle transition. In conclusion, our results suggest that TQ has a potent anti proliferative activity by regulating the G1/S phase cell cycle transition and exhibit a beneficial role in the treatment of HCC.     

Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis

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Protective effect of Sargassum polycystum (brown alga) against acetaminophen-induced lipid peroxidation in rats

Lipid peroxidation is believed to play an important role in the pathogenesis of several diseases, such as cancer, diabetic mellitus and liver injury. Aqueous and ethanol extracts of Sargassum polycystum C. Agardh (Phaeophyta) were screened for their protective effects against acetaminophen (ACP; Paracetamol)-induced lipid peroxidation in rats. A single dose of acetaminophen significantly elevated the levels of lipid peroxides (LPO) with decreased levels of free radical scavenger enzymes (SOD, CAT, GSH, GPx, GST) in liver homogenate. The oral pretreatment of rats with ethanol and aqueous extracts of Sargassum polycystum C. Agardh (100 mg, 200 mg[sol ]kg body wt[sol ]day respectively, for a period of 15 days) significantly reduced the acetaminophen-induced oxidative stress in rats. The animals treated with the ethanol and aqueous extracts alone did not show any toxicity on liver tissue. This observation shows that the seaweed crude extracts probably acted to protect against acetaminophen-induced lipid peroxidation through their free radical scavenging property.     

Effect of squalene on cyclophosphamide-induced toxicity

BACKGROUND: Toxicity due to drugs used for neoplastic disorders is extensively documented. Cyclophosphamide (CYP) is a widely used antineoplastic drug, which could cause toxicity of normal cells due to its toxic metabolites. We evaluated the protective role of squalene (SQ) in the toxicity induced by cyclophosphamide. METHODS: The activities of serum marker enzymes, clinical chemistry parameters and histopathology studies were done according to the standard procedures in the control and experimental groups of rats. RESULTS: Toxicity of the organs like heart, kidney and liver was evidenced from significant (P<0.05) increases of CK, LDH, AST, ALT, ALP, urea, creatinine and total bilirubin in cyclophosphamide- (150 mg/kg for 2 days) administered rats. Abnormal activities of these enzymes in the organs and serum total protein and cholesterol were also observed. No significant changes were observed in triglycerides in serum. Squalene oral treatment exerted protection towards these organs at a dose of 0.4 ml/day/rat. Histopathological examinations also confirmed the protective efficacy of squalene. CONCLUSION: Squalene may be efficacious as a cytoprotectant in cyclophosphamide-induced toxicities.     

Baicalein Abrogates Reactive Oxygen Species (ROS)‐mediated Mitochondrial Dysfunction during Experimental Pulmonary Carcinogenesis In Vivo

Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice, which is exposed to benzo(a)pyrene [B(a)P] for its ability to alleviate mitochondrial dysfunction and systolic failure. Here, we report that oral administration of B(a)P (50 mg/kg body weight)‐induced pulmonary genotoxicities in mice was assessed in terms of elevation in reactive oxygen species (ROS) generation and DNA damage in lung mitochondria. MDA‐DNA adducts were formed in immunohistochemical analysis, which confirmed nuclear DNA damage. mRNA expression levels studied by RT‐PCR analysis of voltage‐dependent anion channel (VDAC) and adenine nucleotide translocase (ANT) were found to be significantly decreased and showed a marked increase in membrane permeability transition pore (MPTP) opening. Accompanied by up‐regulated Bcl‐xL and down‐regulated Bid, Bim and Cyt‐c proteins studied by immunoblot were observed in B(a)P‐induced lung cancer–bearing animals. Administration of BE (12 mg/kg body weight) significantly reversed all the above deleterious changes. Moreover, assessment of mitochondrial enzyme system revealed that BE treatment effectively counteracts B(a)P‐induced down‐regulated levels/activities of isocitrate dehydrogenase, α‐ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, cytochrome‐C‐oxidase and ATP levels. Restoration of mitochondria from oxidative damage was further confirmed by transmission electron microscopic examination. Further analysis of lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C in lung mitochondria was carried out to substantiate the antioxidant effect of BE. The overall data conclude that chemotherapeutic efficacy of BE might have strong mitochondria protective and restoration capacity in sub‐cellular level against lung carcinogenesis in Swiss albino mice.