Protective role of AKBA against benzo(a)pyrene-induced lung carcinogenesis by modulating biotransformation enzymes and oxidative stress.

The present study was designed to explore the chemopreventive potential of 3-acetyl-11-keto-ß-boswellic acid (AKBA) during the initiation and promotion stage of lung carcinogenesis induced by benzo(a)pyrene (BaP) in female Sprague Dawley rats. BaP was administered at a dose level of 50 mg/kg b.wt. twice a week orally in olive oil for 4 weeks. AKBA administration was started 4 weeks before BaP treatment and continued for another 8 weeks at a dose level of 50 mg/kg b.wt. orally in olive oil three times a week. BaP treatment showed significantly increased in the activities of Phase I biotransformation enzymes (Cytochrome P450 , b5 , and aryl hydrocarbon hydrolase) and inhibited the activity of Phase II enzyme (glutathione-S-transferase). Also, a significant elevation in oxidative stress biomarkers lipid peroxidation, reactive oxygen species, and protein carbonyl content concentration. Further, an appreciable decrease was observed in the activities of endogenous antioxidant enzymes superoxide dismutase, CAT, GPx, GR, and a decline in nonenzymatic GSH levels. As a result of BaP induced oxidative stress, alteration in erythrocytes morphology was observed. Fourier transform infrared spectroscopy spectrum of lung tissue showed structural changes due to BaP exposure. Moreover, levels of tumor biomarkers such as total sialic acid, carcinoembryonic antigen, and alkaline phosphatase were significantly elevated following BaP treatment which was substantiated by alterations noticed in the histoarchitecture of lung tissue. Interestingly, AKBA administration to BaP treated rats appreciably alleviated the changes inflicted by BaP on various biochemical indices and histoarchitecture of lungs. Therefore, the study clearly revealed that AKBA by containing oxidative stress shall prove to be quite effective in providing chemoprevention against BaP induced lung carcinogenesis.

Acetyl-11-keto-ß-boswellic acid modulates membrane dynamics in benzo(a)pyrene-induced lung carcinogenesis.

Membrane fluidity is the most important physiochemical property of cell membranes and governs its functional attributes. The current investigations were undertaken to understand the potential role of acetyl-11-keto-ß-boswellic acid (AKBA), if any, on regulation of membrane dynamics under conditions of benzo(a)pyrene (BaP)-induced lung carcinogenesis in female rats. The animals were divided into five groups which included (I) Normal control, (II) Vehicle treated (olive oil), (III) BaP treated, (IV) AKBA treated and (V) BaP + AKBA treated. BaP was administered at a dose level of 50 mg/kg b.wt. in olive oil orally twice a week for 4 weeks. AKBA was given at a dose level of 50 mg/kg b.wt. in olive oil orally thrice a week for 24 weeks. In addition, AKBA was also administered at a similar dose to BaP-treated animals 4 weeks prior to BaP administration and continued for another 20 weeks. The lipid profile and membrane dynamics were analysed in lung tissue. Total lipids, phospholipids content, membrane fluidity, polarization and order of membrane were significantly (p ≤ 0.001) increased in BaP-exposed animals. However, significant decrease was observed in glycolipids, cholesterol, microviscosity and anisotropy levels compared with normal control animals. Appreciable improvements in above indices were recorded when AKBA was administered to BaP-treated animals. Moreover, the structural variations observed in Fourier-transform infrared spectroscopy spectrum were also normalized in BaP-treated rats with AKBA supplementation. This suggests that the AKBA has a potential role in improving membrane fluidity and associated lipid content in BaP-induced lung carcinogenesis.

White tea - A cost effective alternative to EGCG in fight against benzo(a)pyrene (BaP) induced lung toxicity in SD rats.

Tea is a natural resource of catechins and exhibits antioxidative and anticancer activities. This study was designed to elucidate the comparative efficacy of white tea and pure EGCG in containing benzo (a) pyrene (BaP)-induced pulmonary stress. Rats were treated with white tea extract (WT) (1%) and pure EGCG at a dose of 80µg/ml in drinking water on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP(50 mg/kg b. wt) was administered to rats orally in olive oil twice a week for four weeks. The indices such as stress biomarkers (LPO, PCC & ROS), antioxidant enzymes (SOD, CAT, GSH, GST, GR, GPx) activities and lung histoarchitecture were assessed. BaP administration enhanced the levels of inflammatory markers (NO and citrulline) and reduced activities of antioxidant enzymes. We observed similar antioxidant efficacy by both WT and EGCG as seen by their ameliorative action in restoring BaP induced oxidative and inflammatory stress as well as lung histoarchitecture. Our findings suggest that WT is equally beneficial as EGCG in maintaining the integrity of alveoli and is a potential candidate to be used as a cost effective and protective agent in conditions of BaP-induced lung damage.

Evidence of similar protective effects afforded by white tea and its active component 'EGCG' on oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was conducted to unravel the comparative efficacy of White Tea (WT) and Epigallocatechin gallate (EGCG) in affording protection against benzo (a) pyrene (BaP) induced hepatotoxicity. The animals were randomly divided into six groups viz., normal control (NC), BaP, EGCG, WT, WT + BaP and EGCG + BaP treated. 50 mg/kg of BaP was given orally twice a week for 4 weeks. WT extract (1%) and EGCG (1% WT equivalent) were given on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP treated animals showed a significant increase in the activities of biomarkers in conditions of inflammatory, oxidative and liver stress. However, the levels of these biomarkers were decreased appreciably upon treatment with WT and EGCG. Interestingly, no marked differences in these indices were experienced in animals treated with either EGCG or WT. Further, BaP treatment decreased significantly the amount of endogenous antioxidants which however were increased substantially when WT and EGCG were supplemented to BaP treated animals. BaP induced hepatic histoarchitectural alterations also showed an appreciable improvement when these animals were supplemented with WT or EGCG. The present study thus recommends the usefulness of WT extract vis-a -vis EGCG in mitigating BaP induced hepatic dysfunctions.

Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure.

The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na+ K+ ATPase and delta-aminolevulinic acid dehydratase (δ-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na+ K+ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic-contaminated area.

Understanding the role of 3-O-Acetyl-11-keto-ß-boswellic acid in conditions of oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was planned to see whether 3-O-Acetyl-11- keto-ß-boswellic acid has any protective effects against benzo(a)pyrene (BaP) induced toxicity or not. In vitro studies show concentration dependent linear association of radical scavenging activity of AK which is comparable to ascorbic acid taken as reference compound. For in vivo studies, the animals were divided randomly into five groups which included a) normal control, b) vehicle treated (olive oil), c) BaP treated, d) AK treated and e) AK + BaP (combined treated). BaP was administered at a dose of 50mg/kg in olive oil twice a week orally for 4 weeks and AK (50mg/kg) was given in olive oil thrice a week for 4 weeks before and after BaP exposure. BaP treated animals showed a significant increase (p < 0.001) in lipid peroxidation (LPO) and protein carbonyl contents (PCC) in hepatic tissue. Further, a significant increase (p < 0.001) in the liver marker enzymes as well as citrulline and nitric oxide levels in the hepatic tissue was also observed. Interestingly, AK when supplemented to BaP treated animals ameliorated the above said biochemical indices appreciately. The histopathological observations also showed appreciable improvement when BaP treated animals were supplemented with AK, thus emphasing the protective potential of AK.