Inhibitors of poly(ADP-ribose) polymerase show a synergistic potentiation of cytotoxicity with certain DNA-damaging agents. Non-toxic concentrations of 5-methylnicotinamide dramatically potentiate the cytotoxicity of N-methyl-N-nitrosourea as tested by the cloning ability of mouse leukaemia (L1210) cells. A dose-enhancement factor of about 10 is observed. This potentiation is dependent on the concentration of 5-methylnicotinamide. The methylxanthines theobromine, theophylline and caffeine also increase the cytotoxicity of methylnitrosourea. Thymidine, in the presence of sufficient deoxycytidine to overcome the perturbation of deoxynucleotide metabolism, also potentiates the cytotoxicity of methylnitrosourea. Nicotinate, which is not an inhibitor of poly-(ADP-ribose) polymerase, has no effect on methylnitrosourea toxicity.A very small, but consistent, enhancement of the toxicity of y-radiation by the same inhibitors has been observed.We suggest that this potentiation of cytotoxicity is mediated by inhibition of (ADP-ribose), biosynthesis ; and that the biosynthesis is stimulated by DNA damage. We therefore propose that (ADP-ribose), takes part in cellular repair mechanisms, either by modifying chromatin structure or by a specific participation in DNA repair.Poly(ADP-ribose) polymerase is a chromatinbound enzyme which catalyses the synthesis of protein-bound (ADP-ribose), from the coenzyme NAD+ (for reviews see [I, 21). The purified enzyme is totally dependent on both DNA and histones for activity [ 3 ] . The activity of poly(ADP-ribose) polymerase is increased by the production of breaks in DNA induced by both endogeneous [4] and exogencous nucleases A reduction in cellular NAD levels is caused by many alkylating agents [8,9] and also by ionising radiation [lo-121. In earlier studies [I31 we showed that when a nitrosourea (streptozotocin) lowered NAD levels the activity of poly(ADP-ribose) polymerase was increased. We proposed that enhanced activity of the enzyme led to a reduction in cellular DNA levels.We extended the evidence for this hypothesis when we showed that the decrease in NAD level in mouse L1210 leukaemic lymphoblasts treated with N-methyl-N-nitrosourea or with y-radiation is closely correlated with an increase in the activity of poly (ADP-ribose) [5 -71.Abbreviations. ADP-ribose, adenosine(5')diphospho(5)-~-~-ribose; (ADP-ribose),, mixture of ADP-ribose, oligo(ADP-ribose),Enzymes. NAD glycohydrolase (EC 3.2.2.6); poly(ADP-ribose) polymerase polymerase [14]. The drop in cellular NAD was prevented by inhibitors of this enzyme.These inhibitors comprise three classes : nicotinamides and other aromatic amides [15-171, methylxanthines [18 -211 and thymidine and its analogues [16]. The effectiveness of the inhibitors in blocking the lowering of cellular NAD in intact cells mediated by poly(ADP-ribose) polymerase was roughly in line with their relative K , values in isolated nuclei [19]. 5-Methylnicotinamide, theophylline, theobromine and thymidine inhibited the NAD drop caused by 3 krad of y-radiatio...

Aim:To study the effect of chronic exposure of tartarzine at ADI doses on some biochemical parameters of male albino rats. Study Design: The design involved chronic study. In the study, the experiment was divided into phase 1, 2, and 3 which lasted for 30, 60 and 90 days respectively. In each phase, 40 rats were used and were divided into treatment and control groups. The treated groups were given 7.5 mg/kg of tartrazine orally on daily basis over the stipulated periods while the control groups were not treated with tartrazine. Place and Duration of Study:The study was carried out in the within a period of 12 months (December 2017 -December 2018). Methodology: At the end of the chronic study, 5mls of whole blood specimens was collected by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose AJRB, 5(1): 1-14, 2019; Article no.AJRB.50623 2 only). The collected specimens were spun, plasma collected and analyzed for glucose, Lipase, AST, ALT, ALP, total protein, albumin and globulin. Renal, hepatic, and pancreatic tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical analysis was performed using GraphPad Prism version 5.03 (San Diego, California, USA). Results: In the chronic treatment, glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, AST, and ALT showed significantly higher values after 60 of treatment while creatinine, ALP, total protein, albumin and globulin indicated significantly higher values after 90 days of treatment. However, lipase did not show any significant difference after 30, 60, and 90 days of treatment. Histologically, hepatic distortions such as fatty degeneration, vacuolation, pcynosis, and compression of central vein were seen in the liver section. In the renal section, hyaline cast in proximal tubules, hypercellularity of messengial cells, and inflammation of the glomerulus were observed in the treated rats while the histology of the pancreas indicated mild vacuolation of the islet region. However, the pancreatic ducts and acinar cells were not distorted. Conclusion: The administration of tartrazine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, pancreas and kidneys. However, after 60 and 90 days, mild hepatocellular, pancreatic, and renal derangements were seen. Original Research Article

Aim-To assess levels

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Acetaminophen, used for antipyretic and analgesic purposes has been known to exhibit   toxic effects on the organs because of its ability to generate free radicals, causing varieties of diseases. This study investigated the impact of the combined formed of Garcinia kola seed and Vitamin E pretreatment exposure on hepatotoxicity and oxidative stress induced by acetaminophen in Albino Rats. Five groups of animals were used for this study. Group 1 as the control received distilled water orally only, group 2 as toxicity control intoxicated with 800 mg acetaminophen intraperitoneally. The other three groups were pretreated with various doses of either Garcinia kola seed extract or vitamin E or a combined form respectively by oral gavage method for 7 days before induction with acetaminophen intraperitoneally on the 8th day and sacrificed under chloroform anaethesia. Acetaminophen induction significantly rise (p<0.05) the hepatic enzyme levels (ALT, AST, and ALP) and a marked reduction of the antioxidant enzymes (SOD, CAT and GPX) in group 2 animals when compared with the control. There was also a significant rise (p<0.05) in the MDA levels. Meanwhile the combined form of Garcinia kola seed extract and Vitamin E pretreatment exposure on the organs showed no synergetic ameliorative potentials as compared with the single pretreatment exposure with Garcinia kola and Vitamin E respectively. The morphology of the tissue cells pretreated with these combined formed exhibited features showing signs of cell damages and slow recovery from the toxicity. Therefore combining Garcinia kola and Vitamin E may lost its ameliorative and protective effect as seen in this induced acetaminophen albino rats implying that Garcinia kola seed and Vitamin E should not be taken in a combined form.

Background:Lipids and lipoproteins are central to the energy metabolism of the liver, and have continued to be important in clinical practice; basically because of their association with Coronary Heart Disease (CHD). Abnormal lipid metabolism is linked to atherosclerosis due to rising incidence of abdominal obesity.Objective: To evaluate some cardiovascular disease risk status such as lipid profile of pregnant Normotensive and Hypertensive women and compare it with the corresponding levels in Non pregnant Normotensive women.

Aims:To assess the antioxidant effects of the aqueous and ethanolic extracts of Ginger rhizome in testosterone induced prostate hyperplasic male rats. Study Design: The study was a cross-sectional study. Place and Duration of Study: The experimental aspect of this study was conducted at the animal house, Department of Pharmacology, University of Port Harcourt between April and September, 2019. Methodology: Sixty (60) adult albino male wistar rats were used for this study. They were divided into 12 groups of 5 rats each and fed with commercial rat diet and clean drinking water. Aqueous and ethanolic extractions of Ginger rhizome seed were prepared using the maceration method. BPH was induced in rats after they submitted to bilateral orchiectomy by daily injections of Obisike et al.; JOCAMR, 8(2): 1-12, 2019; Article no.JOCAMR.52835 2 testosterone propionate (TP) (4 mg/kg b.wt.sc). Rats were treated with 500 or 1500 mg/kg b.wt. of aqueous or ethanoI extracts of Zingiber officinale (Zo) rhizome, dutasteride or in combination. Administration of extracts was done by gavage. Plasma total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD) activity, were analysed using sandwich ELISA Kits by Shanghai Korain Biotech Co., Ltd, China, while oxidative stress indices (OSI) were calculated. Statistical analysis was done using SPSS version 22.0 of Windows Stat Pac and p values <0.05 were considered statistically significant. Results: The results showed that exogenous induction of BPH in rats significantly increased (p=0.000) plasma TOS and OSI while TAS and SOD activities were reduced. However, 500 and 1500 mg/kg b.wt. of Zo rhizome administered orally after exogenous induction of BPH had been established for 15 days, significantly decreased (p=0.000) TOS, OSI and significantly improved the activities of antioxidant parameters like SOD and TAS. Non-significantly increased mean TAS and SOD were seen in a combination of both extracts with dutasteride, possibly suggestive of synergistic interaction between the herbs and the drug. Simultaneous administration of aqueous and ethanolic extracts of Zo rhizome with TP for 30 days also showed antioxidant qualities, although the effects were statistically not better than values for treatments done when BPH was established before treatment. Ethanolic extracts of Zo rhizome produced better antioxidant effects compared to the aqueous extracts. Conclusion: From the findings, we conclude that Zo rhizome can ameliorate oxidative stress and therefore may be beneficial in the management of benign prostatic hyperplasia. Original Research Article