Potential neuroprotective effect of t-butylhydroquinone against neurotoxicity-induced by 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) in mice.

Dopaminergic damage inducing Parkinson's disease (PD) is ubiquitous neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathways. The etiology and pathogenic factors implicated in dopaminergic damage are still unexplored to develop causal therapeutic strategies aimed to halt its progressive loss. The neurotoxicity induced by 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP), which is more potent neurotoxic than MPTP in mice, is one of the most valuable models for analyzing pathological feature of dopaminergic damage. Herein, we investigated the neuroprotective effect of the potent antioxidant tertiary butylhydroquinone (TBHQ) against 2'CH3-MPTP-induced neurotoxicity in mice as well as the possible mechanism underlying such neurotoxicity. Male albino mice were injected with two doses of 2'CH3-MPTP (20 mg/kg, i.p.) for two consecutive days. Animals were killed after 2 weeks from the last dose of 2'CH3-MPTP. Control animals received 10 mL/kg body weight i.p. of distilled water. In both groups, brain stems containing the nigrostriatal pathways were dissected and reduced glutathione (GSH), malonyldialdehyde (MDA) contents, and superoxide dismutase (SOD) activity were estimated. Also, brain stem histopathological and histochemical changes were examined. The results of this study revealed that i.p. injection of 2'CH3-MPTP caused decrease in the brain stem content of GSH. On the other hand, the content of MDA and SOD activity was increased as compared with control groups. Also, 2'CH3-MPTP showed severe histopathological changes including swelling of cytoplasm, interstitial edema, and complete loss of the neurons with reactive microglial proliferation and gliosis. Furthermore, histochemical examination of brain stem qualitatively showed depletion of dopaminergic neurons of nigrostriatum. Oral administration of TBHQ (100 mg/kg) prior to 2'CH3-MPTP for 7 days caused normalization of GSH content and SOD activity and ameliorated the MDA content but still above the control value. Pretreatment with TBHQ slightly mitigated the histopathological and histochemical changes observed in 2'CH3-MPTP-treated mice. Based on these observations, it can be concluded that the antioxidant TBHQ has the ability to reverse the oxidative stress caused by 2'CH3-MPTP in mice while failed to challenge the histopathological and histochemical changes induced by that toxicant.

Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart.

The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxicity. The implication of natural phenolic acids in the prevention of many pathologic diseases has been reported. Herein, the ability of p-coumaric (PC) acid, a member of phenolic acids, to protect rat's heart against DOX-induced oxidative stress was investigated. Three main groups of albino rats were used; DOX, PC, and PC plus DOX-receiving animals. Corresponding control animals were also used. DOX was administered i.p. in a single dose of 15mgkg(-1). PC alone, in a dose of 100mgkg(-1), was orally administered for five consecutive days. In PC/DOX group, rats received PC 5 days prior to DOX. DOX-induced high serum levels of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), were reduced significantly by PC administration, compared to DOX-receiving rats. Pretreatment with PC ameliorated the cardiac content of glutathione (GSH), and superoxide dismutase (SOD) & catalase (CAT) activities, compared to DOX-receiving rats. On the other hand, accumulation of cardiac content of MDA significantly decreased following PC pretreatment, compared to DOX-treated rats. The data presented here indicate that PC protects rats hearts against DOX-induced oxidative stress in the heart. It may be worthy to consider the usefulness of PC as adjuvant therapy in cancer management.

Possible protective effect of melatonin and/or desferrioxamine against streptozotocin-induced hyperglycaemia in mice.

There is a clear link between diabetes and oxidative stress. Hyperglycaemia leads to free radical generation and alteration of endogenous antioxidants. The present study is an attempt to evaluate the possible protective effect of melatonin (MLT) and/or desferrioxamine (DF) against streptozotocin (STZ)-induced hyperglycaemia in mice. Serum lipid profile, pancreatic tissue contents of glutathione (GSH) and malondialdehyde (MDA) were determined. MLT and/or DF were given p.o. in doses of 5 mg kg(-1)day(-1)and 250 mg kg(-1) day(-1), respectively for 15 consecutive days prior to STZ treatment (60 mg kg(-1) day(-1) i.p.) for 3 consecutive days. Results revealed that STZ induced a marked increase in serum glucose, serum triglycerides (TG), cholesterol (CHO) and LDL-cholesterol. On the contrary HDL-cholesterol was markedly decreased in STZ-treated group. Moreover, STZ induced a significant decrease in the pancreatic content of GSH with concomitant increase in MDA content. Administration of MLT or (MLT+DF) prior to STZ treatment revealed a marked decrease in serum glucose level by 35.6 and 31.6%, respectively as compared to STZ-treated group. Furthermore, MLT pretreatment of STZ-induced hyperglycemic mice, has not only normalized GSH content of pancreatic tissues but also increased its level more than that of control animals by 110%. On the contrary, MDA content of pancreatic tissues was markedly decreased even lower than normal control group. MLT also, induced a marked protection in terms of decreasing serum CHO, LDL, TG by 21.8, 83.8 and 82.2%, respectively, while HDL was increase by 56% as compared to STZ treated group. DF was found to be less effective than MLT in the protection against STZ-induced hyperglycemia. In conclusion, these data suggest that MLT protects against the damaging consequences induced by hyperglycemia either systemically or in the pancreatic tissues.

The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats.

The effect of thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seeds, on the nephropathy and oxidative stress induced by doxorubicin (DOX) in rats was investigated. A single intravenous injection of DOX (6 mg/kg) induced a severe nephrotic syndrome (after 5 weeks) associated with hypoalbuminemia, hypoproteinemia, elevated serum urea, hyperlipidemia, and a high urinary excretion of protein, albumin and N-acetyl-beta-D-glucosaminidase (NAG). In the kidney, DOX induced a significant increase in total triglycerides (TG), total cholesterol (TC), and lipid peroxides and a significant decrease in non-protein sulfhydryl (NPSH) content and catalase (CAT) activity. Treatment of rats with TQ (10 mg/kg per day) supplemented with the drinking water for 5 days before DOX, and daily thereafter, significantly lowered serum urea, TG, and TC. Similarly, TG, TC and lipid peroxides in the kidneys of TQ-treated rats were decreased significantly compared with DOX alone. Moreover, NPSH content and CAT activity in the kidneys of TQ-treated DOX group were significantly elevated compared with DOX alone. Treatment with TQ significantly suppressed DOX-induced proteinuria, albuminuria, and urinary excretion of NAG. The results confirm the involvement of free radicals in the pathogenesis of nephropathy induced by DOX. Likewise, the study demonstrates the high antioxidant potential of TQ and its marked effect on the suppression of DOX-induced nephropathy. The data suggest that TQ might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.

Protective effects of vitamin e and probucol against gentamicin-induced nephrotoxicity in rats.

Gentamicin (GM) is widely used as a bactericidal agent for the treatment of severe gram negative infections, however, its clinical use is partially limited due to its nephrotoxicity. Recent evidence suggests a role of reactive oxygen metabolites in GM nephrotoxicity. The present study was designed to investigate a possible potential protective role of vitamin E and/or probucol against GM nephrotoxicity. GM was administered to rats in a single dose of (150 mg kg(-1)i.p.), while vitamin E (250 mg kg(-1)i.m.) and/or probucol (60 mg kg(-1)i.m.) were given once daily for 3 consecutive days prior to GM administration. GM-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine levels, urinary activity of N-acetyl-beta- d -glucosaminidase (NAG) and gamma-glutamyl-transferase (gamma-GT). Also, GM caused significant increases in kidney content of malondialdehyde (MDA), and significant decreases in kidney content of reduced non-protein sulphydryls (NPSH) and superoxide dismutase (SOD) activity. Vitamin E pretreatment significantly lowered the elevated serum urea and creatinine levels, and urinary activity of NAG and gamma-GT. In addition, vitamin E ameliorated the rise in renal content of MDA and enhanced the renal NPSH content as well as SOD activity. Similarly, probucol significantly inhibited the elevations in urea and creatinine levels and enhanced renal NPSH content and SOD activity. Simultaneous use of vitamin E and probucol was more effective in mitigating disturbances in the assessed parameters. The present work indicates that, due to their antioxidant activity, vitamin E and probucol have potential protective effects against GM nephrotoxicity.

The effect of rate of increase of electrical current on the sensation thresholds of teeth.

The effect of the rate of increase of electrical current during stimulation of human teeth was examined on clinically sound upper anterior teeth. The teeth were stimulated with a current of 10 msec duration at a frequency of 50 Hz. Eight different rates of current increase were used, viz.: 1, 2, 3, 4, 5, 6, 7, and 8 mu a/sec. The results showed that there was a linear relationship between the sensation threshold and the rate of current increase, and that the threshold increased significantly as the rate of current rise increased. Slowly increasing current gave more accurate and reproducible results than did rapidly increasing current, and a rate of 2 mu a/sec was found to be appropriate for clinical pulp-testing.