A combinatorial approach to modulate microenvironment toward regeneration and repair after spinal cord injury in rats.

Traumatic spinal cord injury (SCI) is a devastating condition of CNS which leads to loss of sensory as well as motor functions. Secondary damage after SCI initiates cascade of events that creates an inhibitory milieu for axonal growth and repair. Combinatorial therapies are the hope to attenuate secondary injury progression and make the microenvironment growth and repair friendly for the neurons. We fabricated gelatin- genipin hydrogel system which was impregnated with IONPs and injected at the lesion site in a clinically relevant contusion rat model of SCI. 24 h later, the rats were exposed to magnetic fields (17.96 µT, 50 Hz uniform EMF) for 2 h/day for 5 weeks. A significant (P < 0.001) improvement in Basso, Beattie and Bresnahan (BBB) locomotor score, amplitude and threshold of spinally mediated reflexes and motor and somatosensory evoked potentials (MEP & SSEP) was observed following IONPs implantation and EMF exposure. Moreover, retrograde tracing showed a higher level of neuronal connectivity and survival after the intervention. There was also a reduction in activated microglia and lesion volume which attenuate secondary damage as evident by reduction in the scaring following intervention for 5 weeks. Moreover, we observed increase in the neuronal growth cone marker, GAP-43, growth promoting neurotrophins (GDNF, BDNF & NT-3) and reduction in the inhibitory molecule (Nogo-A) after this combinatorial therapy. We obsrvered that a significant improvement in behavioral, electrophysiological and morphological parameters was due to an alteration in neurotrophin levels, reduction in activated microglia and increase in GAP-43 expression after the combinatorial therapy. We propose that implantation of IONPs embedded gelatin-genipin hydrogel system along with MF exposure modulated the microenvironment, making it conducive for neural repair and regeneration.

Preventive as well as therapeutic significances of linoleic acid in the containment of Leishmania donovani infection.

People suffering from malnutrition show compromised levels of ω-6 fatty acid and malnutrition is frequently observed among visceral leishmaniasis (VL) patients as disease inflicts primarily the socioeconomic destitute communities. Dietary linoleic acid (LA, 18:2; ω-6 fatty acid) is the principal source of essential fatty acid and its derivatives i.e. eicosanoids possess immune-modulatory activities. However, its role in VL is not yet established. LA was measured in VL human subjects (serum) as well as in Leishmania(L.)donovani infected hamsters (serum and visceral organs). Organ-specific mRNA expressions of various enzymes of the LA metabolic pathway were measured in visceral organs of infected hamsters. Our findings showed a decrease in the concentrations of LA in the serum samples of VL patients, suggesting malnutrition among these patients. However, in L. donovani infected hamsters, its level was not altered in the early infection (15 days) and then increased at late infection (60 days). Importantly, the supplementation of LA restored the Th-1 type of immune response and significantly reduced the parasite load within infected macrophages in vitro. This protective response of LA was mediated through 5-lipoxygenase pathway not via the cyclooxygenase pathway. Preventive usage of LA to mϕ followed by L. donovani infection also showed the strengthening of Th-1 immune response and significantly fewer parasite loads. Our findings demonstrate the protective role of LA in the containment of the parasite load. Incorporating LA rich oils in daily food habits across highly inflicted regions may be a significant advancement towards the eradication of the disease.

Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity.

BACKGROUND: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. AIM: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. METHODS: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters. RESULTS: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. CONCLUSION: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.

Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects.

Cisplatin is an effective anti-cancer drug which causes remarkable toxicity to kidney by generating reactive oxygen species and by stimulating inflammatory and apoptotic pathway. Citrus flavonoid, like nobiletin has been reported to possess anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, the present study was aimed to evaluate these properties of nobiletin, a polymethoxy flavone in cisplatin-induced acute renal injury. Adult male albino Wistar rats were divided into 6 groups. Nobiletin was administered at the dose of 1.25, 2.5 and 5mg/kg for a period of 10 days. On 7th day, a single injection of cisplatin (8 mg/kg) was injected to rats. Cisplatin administration resulted in renal dysfunction as evident by increase in serum creatinine and BUN levels. Oxidative stress in cisplatin group was reflected by increase in MDA level, and depletion of anti-oxidants such as glutathione, superoxide dismutase and catalase in renal tissue. Furthermore, cisplatin increased the expressions of Bax, caspase-3 and DNA damage along with decreased expression of Bcl-2 in the renal tissue. Histological analysis also revealed acute tubular necrosis. However, pretreatment with nobiletin preserved renal function and restored anti-oxidant status. Nobiletin supplementation inhibited activation of apoptotic pathways and DNA damage. It also attenuated tubular injury histologically. Collectively, the result of this study suggests the nephroprotective potential of nobiletin which may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

In vitro cytotoxicity and in vivo osseointergration properties of compression-molded HDPE-HA-Al2O3 hybrid biocomposites.

The aim of this study was to investigate the in vivo biocompatibility in terms of healing of long segmental bone defect in rabbit model as well as in vitro cytotoxicity of eluates of compression-molded High density polyethylene (HDPE)-hydroxyapatite (HA)-aluminum oxide (Al2O3) composite-based implant material. Based on the physical property in terms of modulus and strength properties, as reported in our recent publication, HDPE-40 wt % HA and HDPE-20 wt % HA-20 wt % Al2O3 hybrid composites were used for biocompatibility assessment. Osteoblasts cells were cultured in conditioned media, which contains varying amount of composite eluate (0.01, 0.1, and 1.0 wt %). In vitro, the eluates did not exhibit any significant negative impact on proliferation, mineralization or on morphology of human osteoblast cells. In vivo, the histological assessment revealed neobone formation at the bone/implant interface, characterized by the presence of osteoid and osteoblasts. The observation of osteoclastic activity indicates the process of bone remodeling. No inflammation to any noticeable extent was observed at the implantation site. Overall, the combination of in vitro and in vivo results are suggestive of potential biomedical application of compression-molded HDPE- 20 wt % HA- 20 wt % Al2O3 composites to heal long segmental bone defects without causing any toxicity of bone cells.

Immunomodulatory effects of Withania somnifera on azoxymethane induced experimental colon cancer in mice.

The efficacy of Withania somnifera on immunomodulation was tested in experimental azoxymethane induced colon cancer in mice. Azoxymethane is a potential carcinogen to induce the colon cancer in Swiss albino mice. Azoxymethane 15 mg/kg body weight was injected intraperitoneally once a week for 28 days. The colon cancer was confirmed by the appearance of aberrant crypt foci (ACF) in the colons of the experimental mice. The progression in colon tumor development was correlated with the appearance of the histological biomarker and ACF. Azoxymethane induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera extract once a week for four weeks orally. After the experimental period, the animals were sacrificed and analyzed for immunocompetent cells, immune complexes and immunoglobulins. W. somnifera significantly altered the level of leucocytes, lymphocytes, neutrophils, immune complexes and immunoglobulins (Ig) A, G and M. The azoxymethane induced colon cancer and immune dysfunction was better controlled by W. somnifera. These results suggested that the immunomodulatory effects of W. somnifera could be useful in the treatment of colon cancer.

Modulating effect of Withania somnifera on TCA cycle enzymes and electron transport chain in azoxymethane-induced colon cancer in mice.

The aim of the present investigation was to evaluate the efficacy of Withania somnifera on tricarboxylic acid (TCA) cycle enzymes and electron transport chain in azoxymethane-induced experimental colon cancer in mice. Azoxymethane at the dose of 15 mg/kg body weight was induced intraperitoneally once in a week for 28 days. The progression in colon tumor development was correlated with the appearance of the histological biomarker and aberrant crypt foci (ACF). Azoxymethane-induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera once in a week orally for 28 days. After the experimental period, the animals were killed and analyzed for TCA cycle key enzymes, such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and alpha-keto glutarate dehydrogenase (alpha-KGDH). The modulating effect of W. somnifera on TCA cycle key enzymes and electron transport chain complexes were investigated against colon cancer induced by azoxymethane in Swiss albino mice. Decreased activities of TCA cycle key enzymes such as ICDH, SDH, MDH, and alpha-KGDH in colon cancer bearing animals were observed. W. somnifera administration normalized these enzyme levels in azoxymethane-induced experimental mice. These results suggested that W. somnifera is the promising chemotherapeutic agent for the treatment of colon cancer.

Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma.

BACKGROUND: Disturbance in the delicate balance between L-arginine-metabolizing enzymes such as nitric oxide synthase (NOS) and arginase may lead to decreased L-arginine availability to constitutive forms of NOS (endothelial NOS), thereby increasing the nitro-oxidative stress and airway hyperresponsiveness (AHR). OBJECTIVE: In this study, we investigated the effects of high doses of L-arginine on L-arginine-metabolizing enzymes and subsequent biological effects such as cyclic guanosine monophosphate production, lipid peroxidation, peroxynitrite, AHR, and airway inflammation in a murine model of asthma. METHODS: Different doses of L-arginine were administered to ovalbumin-sensitized and challenged mice. Exhaled nitric oxide, AHR, airway inflammation, T(H)2 cytokines, goblet cell metaplasia, nitro-oxidative stress, and expressions of arginase 1, endothelial NOS, and inducible NOS in lung were determined. RESULTS: L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T(H)2 cytokines, TGF-beta1, goblet cell metaplasia, and subepithelial fibrosis. Further, L-arginine increased ENO levels and cyclic guanosine monophosphate in lung and reduced the markers of nitro-oxidative stress such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. This was associated with reduced activity and expression of arginase 1, increased expression of endothelial NOS, and reduction of inducible NOS in bronchial epithelia. CONCLUSION: We conclude that L-arginine administration may improve disordered nitric oxide metabolism associated with allergic airway inflammation, and alleviates some features of asthma.

Impact of magnetic nanoparticles in biomedical applications.

In the recent years, there has been a growing interest in the development of nanoparticles based targeting agents for the tumor diagnostics and therapeutics. This is because of their potential to detect the tumor and treat the diseased tissue at the cellular and molecular level. In this respect nanoscale magnetic materials have shown a very promising therapeutic concept and offer a new perspective for the diagnostic and target drug delivery approach. The magnetic nanocarriers have the ability to accumulate at any desired pharmacological site just by the guidance of external magnetic field. But, the interactions of these magnetic nanocarriers with the biological environment are rare and depend largely upon their surface chemistry and size. To increase the interactions and achieve the desired pharmaceutically acceptable delivery system, the surface of magnetic nanocarriers is modified in various ways by coating with organic polymers and inorganic metals or oxides. On the basis of surface characteristics, a number of effective magnetically driven therapies have been proposed by many researchers and protected through patents time to time.

Glycyrrhizin alleviates experimental allergic asthma in mice.

Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.

Effect of dietary palm olein oil on oxidative stress associated with ischemic-reperfusion injury in isolated rat heart.

BACKGROUND: Palm olein oil (PO), obtained from refining of palm oil is rich in monounsaturated fatty acid and antioxidant vitamins and is widely used as oil in diet in many parts of the world including India. Palm oil has been reported to have beneficial effects in oxidative stress associated with hypertension and arterial thrombosis. Oxidative stress plays a major role in the etiopathology of myocardial ischemic-reperfusion injury (IRI) which is a common sequel of ischemic heart disease. Antioxidants have potent therapeutic effects on both ischemic heart disease and ischemic-reperfusion injury. Information on the effect of PO on ischemic-reperfusion injury is, however, lacking. In the present study, the effect of dietary palm olein oil on oxidative stress associated with IRI was investigated in an isolated rat heart model. Wistar rats (150-200 gm) of either sex were divided into three different groups (n = 16). Rats were fed with palm olein oil supplemented commercial rat diet, in two different doses [5% v / w (PO 5) and 10% v / w (PO 10) of diet] for 30 days. Control rats (C) were fed with normal diet. After 30 days, half the rats from each group were subjected to in vitro myocardial IRI (20 min of global ischemia, followed by 40 min of reperfusion). Hearts from all the groups were then processed for biochemical and histopathological studies. One way ANOVA followed by Bonferroni test was applied to test for significance and values are expressed as mean +/- SE (p < 0.05). RESULTS: There was a significant increase in myocardial catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities with no significant change in myocardial thiobarbituric acid reactive substances (TBARS) only in group PO 5 as compared to group C. There was no light microscopic evidence of tissue injury. A significant rise in myocardial TBARS and depletion of myocardial endogenous antioxidants (SOD, CAT and GPx) along with significant myocyte injury was observed in control rats subjected to ischemia-reperfusion (C IR). Hearts from palm olein oil fed rats subjected to ischemia-reperfusion (PO 5 IR and PO 10 IR) were protected from increase in TBARS and depletion of endogenous antioxidants as compared to C IR group. No significant myocyte injury was present in the treated groups. CONCLUSIONS: The present study demonstrated for the first time that dietary palm olein oil protected rat heart from oxidative stress associated with ischemic-reperfusion injury.

Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms.

The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.

Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment.

The efficacy of Withania somnifera (Ws) to limit myocardial injury after ischemia and reperfusion was explored and compared to that of Vit E, a reference standard known to reduce mortality and infarct size due to myocardial infarction. Wistar rats (150-200 g) were divided into six groups and received orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were monitored. Hearts were removed and processed for histopathological and biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated. Postischemic reperfusion produced significant cardiac necrosis, depression of left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as an increase in MDA level (p < 0.05) in the control group rats as compared to sham group. The changes in levels of protein and GPx was however, not significant. Ws and Vit E favorably modulated most of the hemodynamic, biochemical and histopathological parameters though no significant restoration in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the synthesis of endogenous antioxidants compared to sham. Results indicate that Ws significantly reduced myocardial injury and emphasize the beneficial action of Ws as a cardioprotective agent.

Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction.

The present study was designed to evaluate the cardioprotective potential of hydro-alcoholic extract of Withania somnifera on the basis of haemodynamic, histopathological and biochemical parameters in the isoprenaline-(isoproterenol) induced myocardial necrosis in rats and to compare with Vitamin E, a known cardioprotective antioxidant. Wistar albino male rats (150-200 g) were divided into six main groups: sham, isoprenaline control, Withania somnifera/Vitamin E control and Withania somnifera/Vitamin E treatment groups. Withania somnifera was administered at doses 25, 50 and 100 mg/kg and Vitamin E at a dose of 100 mg/kg, orally for 4 weeks. On days 29 and 30, the rats in the isoprenaline control and Withania somnifera/Vitamin E treatment groups were given isoprenaline (85 mg/kg), subcutaneously at an interval of 24 hr. On day 31, haemodynamic parameters were recorded and the hearts were subsequently removed and processed for histopathological and biochemical studies. A significant decrease in glutathione (P<0.05), activities of superoxide dismutase, catalase, creatinine phosphokinase and lactate dehydrogenase (P<0.01) as well as increase in lipid peroxidation marker malonyldialdehyde level (P<0.01) was observed in the hearts of isoproterenol control group rats as compared to sham control. However, we have not observed any significant changes in activity of glutathione peroxidase and protein levels. Left ventricular dysfunction was seen as a decrease in heart rate, left ventricular rate of peak positive and negative pressure change and elevated left ventricular end-diastolic pressure in the control group was recorded. On histopathological examination, myocardial damage was further confirmed. Our data show that Withania somnifera (25, 50 and 100 mg/kg) exerts a strong cardioprotective effect in the experimental model of isoprenaline-induced myonecrosis in rats. Augmentation of endogenous antioxidants, maintenance of the myocardial antioxidant status and significant restoration of most of the altered haemodynamic parameters may contribute to its cardioprotective effect. Among the different doses studied, Withania somnifera at 50 mg/kg dose produced maximum cardioprotective effect.

Protection against acute adriamycin-induced cardiotoxicity by garlic: role of endogenous antioxidants and inhibition of TNF-alpha expression.

BACKGROUND: Oxidative stress is the major etiopathological factor in adriamycin-induced cardiotoxicity. Relatively low amounts of endogenous antioxidant makes the heart vulnerable to oxidative stress-induced damage. Chronic oral administration of garlic has been reported to enhance the endogenous antioxidants of heart. We hypothesized that garlic-induced enhanced cardiac antioxidants may offer protection against acute adriamycin-induced cardiotoxicity. RESULTS: Rats were either administered freshly prepared garlic homogenate (250 and 500 mg/kg daily, orally, for 30 days) or probucol (cumulative dose, 120 mg/kg body weight divided in 12, i.p. over a period of 30 days) or double distilled water (vehicle), followed by a single dose of adriamycin (30 mg/kg i.p.). In the adriamycin group, increased oxidative stress was evidenced by a significant increase in myocardial TBARS (thiobarbituric acid reactive substances) and decrease in myocardial SOD (superoxide dismutase), catalase and GPx (glutathione peroxidase) activity. Histopathological studies showed focal as well as subendocardial myocytolysis with infiltration of macrophages, lymphocytes and edema. Immunocytochemistry showed marked expression of TNF-alpha (tumor necrosis factor-alpha) in the myocardium. Increase in myocardial TBARS and decrease in endogenous antioxidants by adriamycin was prevented significantly in the garlic treated rat hearts, which was comparable to the probucol-treated group. Histopathological evidence of protection was also evident in both garlic-treated and probucol-treated groups. Probucol, 250 mg/kg and 500 mg/kg of garlic reduced adriamycin induced TNF-alpha expression in the myocardium and was associated with reduced myocyte injury. CONCLUSIONS: It is concluded that chronic garlic administration prevents acute adriamycin-induced cardiotoxicity and decreases myocardial TNF-alpha expression.

Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of skin in Swiss albino mice.

The chemopreventive effect of Withania somnifera hydroalcoholic root extract (WSRE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was investigated in Swiss albino mice. The skin lesions were induced by the twice-weekly topical application of DMBA (100 nmol/ 100 microliters acetone) for 8 wk on the shaved back of mice. WSRE was administered at the maximal tolerated dose of 400 mg/kg p.o. three times per week on alternate days 1 wk before DMBA and continued for 24 wk thereafter. The results of the study revealed a significant decrease in incidence and average number of skin lesions in mice compared with DMBA alone at the end of Week 24. Biochemical parameters were assessed in the lesions of WSRE-treated and untreated control mice. A significant impairment was noticed in the levels of reduced glutathione, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase in skin lesions of DMBA-treated control mice compared with vehicle-treated mice. These parameters were returned to near normal by administration of WSRE to DMBA-treated mice. The above findings were supported by histopathological studies. From the present study, it can be inferred that WRSE possesses potential chemopreventive activity in this experimental model of cancer. The chemopreventive activity may be linked to the antioxidant/free radical-scavenging constituents of the extract. The anti-inflammatory and immunomodulatory properties of WSRE are also likely to contribute to its chemopreventive action.

Chronic garlic administration protects rat heart against oxidative stress induced by ischemic reperfusion injury.

BACKGROUND: Oxidative stress plays a major role in the biochemical and pathological changes associated with myocardial ischemic-reperfusion injury (IRI). The need to identify agents with a potential for preventing such damage has assumed great importance. Chronic oral administration of raw garlic has been previously reported to augment myocardial endogenous antioxidants. In the present study, the effect of chronic oral administration of raw garlic homogenate on oxidative stress induced by ischemic-reperfusion injury in isolated rat heart was investigated. RESULTS: Raw garlic homogenate (125, 250 and 500 mg/kg once daily for 30 days) was administered orally in Wistar albino rats. Thereafter, hearts were isolated and subjected to IRI (9 min. of global ischemia, followed by 12 min of reperfusion; perfusion with K-H buffer solution; 37 degrees C, 60 mm Hg.). Significant myocyte injury and rise in myocardial TBARS along with reduction in myocardial SOD, catalase, GSH and GPx were observed following IRI. Depletion of myocardial endogenous antioxidants and rise in TBARS were significantly less in the garlic-treated rat hearts. Oxidative stress induced cellular damage as indicated by ultrastructural changes, like disruption of myofilament, Z-band architecture along with mitochondrial changes were significantly less. CONCLUSIONS: The study strongly suggests that chronic garlic administration prevents oxidative stress and associated ultrastructural changes, induced by myocardial ischemic-reperfusion injury.