Lysosomal abnormalities during benzo(a)pyrene‐induced experimental lung carcinogenesis – defensive role of capsaicin

Abstract

The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, beta-D-glucosidase, beta-D-galactosidase, beta-D-glucuronidase, beta-D-N-acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis.

Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene

“…DT‐diaphorase (DTD) is a flavoprotein that catalyzes the two electron reduction of quinones and other nitrogen oxides . This reaction prevents one electron redox cycling of these groups, thereby inhibiting the formation of DNA damaging ROS . In our present study, a substantial increase in lung phase I enzymes was observed in the carcinogen‐treated animals, which was reversed following BE treatment.…”

“…Electron microscopic analysis of B(a)P‐treated lung sections showed complete loss of architecture in lysosomes of cancer‐bearing animals indicating lysosomal damages. The defects in lysosomal architecture would lead to the alterations in the lysosomal metabolism, resulting in decreased activities of lysosomal enzymes in the B(a)P‐induced lung, thus becoming a key contributor to intrinsic cell dysfunction . The near‐normal appearance of the lung tissue on supplementation with BE shows the protective effect of BE in B(a)P‐induced disruption of lysosomal fine structure.…”

A Comprehensive Review of the Carcinogenic and Anticarcinogenic Potential of Capsaicin

“…For instance, capsaicin prevented pronounced oxidative damage caused by BP to biomolecules, preserved lysosomal stability, restored the activities of phase I and II biotransformation enzymes and the levels of tumor markers to near normalcy. BP-induced lung cancer animals showed abnormal changes in body weight, tumor incidence, low blood glucose and alterations in lipid levels, all of which were significantly reversed by capsaicin (Anandakumar et al 2008;Anandakumar et al 2008aAnandakumar et al , 2008bAnandakumar et al2009aAnandakumar et al , 2009b; Anandakumar, P., Kamaraj, S., Jagan, S., Ramakrishnan, G., Naveenkumar, et al 2009). …”

“…twice weekly for 4 weeks increased lysosomal enzyme activities and oxidative stress, altered phase I and II enzymes, increased serum tumor markers, changed body weight, and tumor incidences Capsaicin (10 mg/kg, i.p.) 1 week prior to first BP dose for 14 weeks generally reversed all reported BP-induced changes, attenuated abnormalities and restored normal values Anandakumar et al 2008;Anandakumar et al 2008aAnandakumar et al , 2008bAnandakumar et al2009aAnandakumar et al , 2009b; Anandakumar, P., Kamaraj, S., Jagan, S., Ramakrishnan, G., Naveenkumar, et al 2009 B6 mice DMBA-initiated and TPA-promoted TRPV1 WT mice showed more tumors than KO mice DMBA-initiated mice showed no tumors with topical capsaicin applications Capsaicin co-administration enhanced TPA-promoted tumors Bode et al 2009;Hwang et al 2010 papillary or nodular hyperplasia of the urinary bladder. Incidences of carcinogen-induced lesions of the thyroid and kidney were not significantly altered by capsaicin.…”

“…At the termination of the study (38 weeks), capsaicin feeding during either the initiation or promotion phase reduced the frequency of tongue squamous cell papillomas and squamous cell carcinomas (NQO alone, 9/15 rats with tongue tumors; NQO plus 10 weeks capsaicin, 5/17 rats with tongue tumors [not significant]; NQO plus 28 weeks of capsaicin, 3/14 rats with tongue tumors [p<0.05]). In a series of closely related experiments using Swiss albino mice, capsaicin was shown to exert its chemoprotective effects via several different mechanisms against benzo(a)pyrene (BP)-induced lung cancer (Anandakumar et al 2008;Anandakumar et al 2008aAnandakumar et al , 2008bAnandakumar et al2009aAnandakumar et al , 2009b; Anandakumar, P., Kamaraj, S., Jagan, S., Ramakrishnan, G., Naveenkumar, et al 2009). Due to the closely related nature of methods and somewhat overlapping results, key results from all 8 publications are grouped into one entry in Table 4.…”