Anticancer potential of Tinospora cordifolia and arabinogalactan against benzo(a)pyrene induced pulmonary tumorigenesis: a study in relevance to various biomarkers

Introduction: Aqueous Tinospora cordifolia stem extract (Aq.Tc) and arabinogalactan (AG), its bioactive polysaccharide, which are antioxidant remedies were evaluated on pulmonary cancer and associated tumor markers. Methods: Mice were randomly segregated into 6 groups. Group I: animals served as control. Group II: animals which were administered Aq.Tc extract (200 mg/kg, orally), thrice a week. Group III: animals which received AG (7.5 mg/kg, orally) thrice a week. Group IV: animals which were instilled with benzo(a)pyrene (B(a)P) (50 mg/kg, orally) twice within an interval of 2 weeks. Group V: animals which received Aq.Tc extract as in group II, along with B(a)P after 2 weeks of Aq.Tc administration. Group VI: animals which received AG as in group III along with B(a)P after 2 weeks of AG administration. Results: As expected, B(a)P treated mice exhibited high tumor incidence and multiplicity with concomitant increase in serum/plasma markers like carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH) and tumor necrosis factor. However, Aq.Tc and AG supplementation to B(a)P abused animals significantly attenuated these parameters at different stages of cancer, depicting their anti-cancer effects in lung carcinogenesis. Also, treatment of Aq.Tc and AG to tumor bearing mice reduced the degree of histopathological alterations as compared to B(a)P installed mice. The apoptotic index in case of Aq.Tc and AG fed mice treated with B(a)P was higher as compared to only B(a)P treated mice. Further it was observed that Aq.Tc could induce higher degree of apoptosis when compared to AG group, suggesting Aq.Tc as a more effective modulator of tumorigenesis. Conclusion: Overall, these findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Aq.Tc was found to be more effective than AG in modulating the process of lung carcinogenesis as reflected by various observations

Effect of alpha-tocopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice

BACKGROUND: Free radicals generated in biological systems by cigarette smoke (CS) inhalation can cause oxidative stress in tissues, resulting in lipid peroxidation (LPO). In view of the antioxidant properties of α-tocopherol (AT), in the present study, effects of AT on antioxidant defence system and LPO were investigated in mice inhaling CS for different time intervals. RESULTS: Male Balb/c mice were fed orally with AT (5 I.U./Kg.b.wt.) and /or exposed to CS for 2, 4, 6 or 8 weeks. No effect was observed on body growth, diet consumption, water intake and lung weight due to AT and /or CS treatment in any of the groups as compared to their control counterparts. After two weeks of treatment, no change in LPO, reduced glutathione (GSH) levels and antioxidant enzymes were observed except for glutathione reductase (GR) which increased in all the treated groups. A significant increase in pulmonary LPO levels was observed in mice exposed to CS inhalation for 4, 6 or 8 weeks. There was a gradual increase in the LPO levels as the extent of CS inhalation increased from 4 to 8 weeks. However, the extent of increase in LPO levels due to CS exposure for 4, 6 or 8 weeks in the mice treated with AT was comparatively less. A significant decrease in the GSH levels was also observed in all the animals exposed to CS for 4, 6 or 8 weeks. There was a significant increase in the activities of catalase, glutathione peroxidase (GSH-Px) and GR observed in all the groups exposed to CS for 4,6 or 8 weeks. The increase in above antioxidant enzymes seems to be insufficient to combat the oxidative stress posed by CS inhalation. There was a marked decrease observed in the LPO levels in the animals treated with AT alone for 4, 6, or 8 weeks, when compared to their control counterparts. However, the supplementation of AT for 4, 6 or 8 weeks demonstrated a significant increase in GSH levels. CONCLUSION: It appears from our studies that AT exhibits its antioxidant role either directly by scavenging the oxidative species or indirectly by modulating the GSH levels

Tinospora cordifolia (Willd.) Hook. f. and Thoms. and Arabinogalactan exert chemopreventive action during B(a)P induced pulmonary carcinogenesis: Studies on ultrastructural, molecular and biochemical alterations

Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Tc) is a medicinal plant gaining considerable attention owing to its wide range of pharmacological properties. Though there are ample reports which have documented its biological activity in various clinical disorders, there is a paucity of information regarding its anticancer activity particularly against B(a)P induced lung cancer. So, the present study evaluates the chemopreventive potentials of aqueous extract of Tc (Aq.Tc) and its active component; Arabinogalactan (AG) against Benzo(a)pyrene [B(a)P] induced pulmonary carcinogenesis in BALB/c mice. B(a)P resulted in significant alteration in carcinogen metabolizing enzymes (CME’s), reduced glutathione and lipid peroxidation levels. B(a)P also inflicted clastogenic damage, disturbed phospholipid saturation, protein secondary structures and glycogen content. Altogether these events resulted in the alterations in cellular arrangement of pulmonary tissue, depicting the outburst of lung carcinogenesis. However, Aq.Tc and AG significantly helped to normalize the disturbed levels of CME’s and antioxidant machinery. Clastogenic changes, phospholipid saturation, protein secondary structures and glycogen content were also alleviated with Aq.Tc and AG administration. Additionally, B(a)P+ Aq.Tc and B(a)P + AG treated groups revealed the classical features of apoptosis. The results suggest that the aquatic extract of gudichi (Aq.Tc) and Arabinogalactan (AG) modulate various key processes associated with carcinogenesis and can be used as effective chemopreventive agents

Tinospora cordifolia (Willd.) Hook. f. and Thoms. and Arabinogalactan exert chemopreventive action during B(a)P induced pulmonary carcinogenesis: Studies on ultrastructural, molecular and biochemical alterations

671-687Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Tc) is a medicinal plant gaining considerable attention owing to its wide range of pharmacological properties. Though there are ample reports which have documented its biological activity in various clinical disorders, there is a paucity of information regarding its anticancer activity particularly against B(a)P induced lung cancer. So, the present study evaluates the chemopreventive potentials of aqueous extract of Tc (Aq.Tc) and its active component; Arabinogalactan (AG) against Benzo(a)pyrene [B(a)P] induced pulmonary carcinogenesis in BALB/c mice. B(a)P resulted in significant alteration in carcinogen metabolizing enzymes (CME’s), reduced glutathione and lipid peroxidation levels. B(a)P also inflicted clastogenic damage, disturbed phospholipid saturation, protein secondary structures and glycogen content. Altogether these events resulted in the alterations in cellular arrangement of pulmonary tissue, depicting the outburst of lung carcinogenesis. However, Aq.Tc and AG significantly helped to normalize the disturbed levels of CME’s and antioxidant machinery. Clastogenic changes, phospholipid saturation, protein secondary structures and glycogen content were also alleviated with Aq.Tc and AG administration. Additionally, B(a)P+ Aq.Tc and B(a)P + AG treated groups revealed the classical features of apoptosis. The results suggest that the aquatic extract of gudichi (Aq.Tc) and Arabinogalactan (AG) modulate various key processes associated with carcinogenesis and can be used as effective chemopreventive agents

Aloe vera modulates X-ray induced bone mineral loss and other deleterious effects on various tissues of mice

The present study was designed to examine the effects of Aloe vera on whole body X-ray exposure induced injury to heart, lung, and bone of male balb/c mice. Animals were divided into four groups: control, Aloe vera (50 mg/kg body weight on alternate days for 30 days), X-ray (2Gy) and Aloe vera+ X-ray. X-ray irradiation led to enhanced lipid peroxidation level associated with decline in reduced glutathione concentration in pulmonary tissue of mice. Moreover, lipid peroxidation level and reduced glutathione content in cardiac tissue remained unaltered after radiation exposure. In addition, X-ray exposure caused poor and delayed uptake of 99mTc-mebrofenin as observed in hepatobiliary clearance study. Dual energy X-ray absorptiometry scan revealed a significant decrease in bone mineral density after X-ray irradiation. Aloe vera administration to radiation exposed animals restored pulmonary reduced glutathione content and lipid peroxidation level along with significantly improved bone mineral density and hepatobiliary clearance profile as compared to irradiated counterparts. The current observations suggest that Aloe vera plays vital role in modulating deleterious effects caused by X-ray exposure in various organs of mice, which may attributed its free radical scavenging ability and strengthening of antioxidant defense system

Celecoxib mitigates cigarette smoke induced oxidative stress in mice

285-291Cigarette smoke (CS) is a rich source of radicals, predisposing the cell to oxidative stress resulting in inflammation. Chronic inflammation is a recognized risk factor for carcinogenesis. Cyclooxygenase-2 (COX-2) is a mediator of inflammatory pathway and may, therefore, contribute to carcinogenesis. There are several reports that suggest the association between CS and COX-2 associated risk to cancer. In the present study, we examined the role of celecoxib (a selective COX-2 inhibitor) in modulating the oxidative stress caused by CS inhalation in mice. CS exposure for a period of 10 weeks caused oxidative stress in the pulmonary and hepatic tissues, as evident from the increase in lipid peroxidation levels (LPO) and decrease in reduced glutathione (GSH) levels. Celecoxib (125 mg/kg body weight for 8 weeks) administration to CS inhaling mice reduced the oxidative stress by decreasing the LPO levels and enhancing the GSH levels in comparison to the CS-exposed group. CS exposure repressed the enzymatic antioxidant defense system, as evident from the decrease in catalase (CAT) and superoxide dismutase (SOD) activities. Co-adminstration of celecoxib considerably reversed the changes in the enzymatic antioxidant defense system. Histopathological studies of lungs showed that CS exposure induced alveolar wall destruction and air space enlargement. In co-treated group, the alveolar septa were thicker than normal with apparent infiltration of inflammatory cells. In CS-exposed group, hepatic tissue exhibited vacuolization and macrophage infiltration. Co-treatment with celecoxib restored the normal histoarchitechture in hepatic tissues of CS inhaling mice. Thus, the present study demonstrated that celecoxib adminstration reduced the oxidative stress-mediated risk to carcinogenesis, due to its ability to boost the antioxidant defense system

Anticancer potential of Tinospora cordifolia and arabinogalactan against benzo(a)pyrene induced pulmonary tumorigenesis: a study in relevance to various biomarkers

Introduction: Aqueous Tinospora cordifolia stem extract (Aq.Tc) and arabinogalactan (AG), its bioactive polysaccharide, which are antioxidant remedies were evaluated on pulmonary cancer and associated tumor markers. Methods: Mice were randomly segregated into 6 groups. Group I: animals served as control. Group II: animals which were administered Aq.Tc extract (200 mg/kg, orally), thrice a week. Group III: animals which received AG (7.5 mg/kg, orally) thrice a week. Group IV: animals which were instilled with benzo(a)pyrene (B(a)P) (50 mg/kg, orally) twice within an interval of 2 weeks. Group V: animals which received Aq.Tc extract as in group II, along with B(a)P after 2 weeks of Aq.Tc administration. Group VI: animals which received AG as in group III along with B(a)P after 2 weeks of AG administration. Results: As expected, B(a)P treated mice exhibited high tumor incidence and multiplicity with concomitant increase in serum/plasma markers like carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH) and tumor necrosis factor. However, Aq.Tc and AG supplementation to B(a)P abused animals significantly attenuated these parameters at different stages of cancer, depicting their anti-cancer effects in lung carcinogenesis. Also, treatment of Aq.Tc and AG to tumor bearing mice reduced the degree of histopathological alterations as compared to B(a)P installed mice. The apoptotic index in case of Aq.Tc and AG fed mice treated with B(a)P was higher as compared to only B(a)P treated mice. Further it was observed that Aq.Tc could induce higher degree of apoptosis when compared to AG group, suggesting Aq.Tc as a more effective modulator of tumorigenesis. Conclusion: Overall, these findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Aq.Tc was found to be more effective than AG in modulating the process of lung carcinogenesis as reflected by various observations

Azadirachta indica leaf extract modulates initiation phase of murine forestomach tumorigenesis

209-215The effects of aqueous Azadirachta indica leaf extract (AAILE) on benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis, B(a)P-DNA adduct formation and certain parameters of carcinogen biotransformation system in mice have been reported earlier from our laboratory. In this study, the effects of AAILE on the enzymes of B(a)P biotransformation, which play crucial role in initiation of chemical carcinogenesis aryl hydrocarbon hydroxylase (AHH) and uridinediphosphoglucuronosyltransferase (UDP-glucuronosyltransferase) have been evaluated in murine forestomach and liver. In addition, lipid peroxidation (LPO) levels in forestomach as well as liver and the activities of tissue injury marker enzymes lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase in the serum have also been evaluated. Oral administration of AAILE (100 mg/kg body wt for 2 weeks) reduces the AHH activity and enhances the UDP-glucuronosyltransferase activity in both the tissues, suggesting its potential in decreasing the activation and increasing the detoxification of carcinogens. The LPO levels decrease upon AAILE treatment in the hepatic tissue, suggesting its anti-oxidative and hence anti-carcinogenic effects. Non-significant alterations have been observed in tissue injury marker enzymes upon AAILE treatment, suggesting its safety at the given dose. In conclusion, AAILE appears to modulate initiation phase of carcinogenesis and may be suggested as safe and an effective agent for chemoprevention

Phytomodulatory potential of lycopene from <i style="mso-bidi-font-style:normal">Lycopersicum esculentum</i> against doxorubicin induced nephrotoxicity

635-645An elevated level of serum urea and creatinine was observed in doxorubicin (DOX) treated animals indicating DOX-induced nephrotoxicity. Enhanced lipid peroxidation (LPO) in the renal tissue was accompanied by a significant decrease in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. Administration of lycopene (LycT) extracted from tomato to DOX treated mice showed a significant reduction in serum creatinine and urea levels which were associated with significantly low levels of LPO and significantly enhanced level of GSH and related antioxidant enzymes activity (GPx, GR and CAT) when compared to DOX group. Histopathological analysis revealed severe damage in the renal tissue of DOX treated animals. However, animals pretreated with LycT were observed to have reduced damage. Thus, from present results it may be inferred that lycopene may be beneficial in mitigating DOX induced nephrotoxicity in mice