Ashwani Koul

In light of the increasing exposure to folate and its unresolved relationship with skin cancer, experimental studies are warranted to better understand and define its role in skin carcinogenesis. The present study evaluated the effects of folic acid supplementation on cutaneous squamous cell carcinoma (cSCC) in mice and explored the underlying mechanisms. A two‐stage skin carcinogenesis model was employed using 7,12‐dimethylbenz[a]anthracene (DMBA) and 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA) as initiator and tumor promoter respectively. LACA mice were orally supplemented with folic acid (FA) at doses of 1 or 2 mg/kg body weight and divided into six groups: control, DMBA/TPA, FA1(1 mg/kg) + DMBA/TPA, FA2(2 mg/kg) + DMBA/TPA, FA1 and FA2 groups. Supplementation began 4 weeks prior to tumor induction and continued for twenty weeks. Histopathological analysis confirmed cSCC development. During the early stages, papilloma incidence was higher in FA1 + DMBA/TPA and FA2 + DMBA/TPA groups in comparison to DMBA/TPA group. However, by the end of the treatment period, lesion incidence reached 100% in all groups, with a greater total lesion count and lesion burden observed in the supplemented groups its indicating pro‐carcinogenic effects. Enhanced cellular proliferation in these groups was evident from histomorphometric assessments and increased expression of proliferating cell nuclear antigen and folate transporters. Increase in tumorigenesis was also associated with enhanced activity of serum lactate dehydrogenase, oxidative DNA damage and inhibition in expression of MGMT gene. However, no noteworthy difference was observed between two levels of supplementation. These findings suggest that folic acid supplementation may promote skin tumorigenesis through increased proliferation, enhanced DNA damage, and impaired DNA repair mechanisms.

The present study was designed to assess the modulatory effects of Aloe vera on chromium-induced alterations in renal and testicular tissues of mice. For this study, male Balb/c were divided into four groups: Group I (control), Group II (PD) [orally administered with potassium dichromate], group III (AV) [orally administered with Aloe vera] and group IV (AV+PD) [administered with Aloe vera and potassium dichromate]. Histopathological alterations and levels of renal (urea, blood urea nitrogen, uric acid, creatinine) and testicular (sperm count and motility) organ function markers indicated damage to these organs. This was accompanied by increased serum lactate dehydrogenase activity. Chromium appeared to weaken the DNA repair machinery of the cells, as observed from the decrease in mRNA expression of DNA-PK and MGMT genes in renal tissue. Improvement in histoarchitecture and functional markers of organs, decrease in cell damage marker, and increased expression of DNA repair-associated genes are indicative of protection rendered by A. vera against chromium-induced harmful effects. This preliminary study indicates the beneficial effects of A. vera against heavy metal toxicity. However, it is imperative to exhaustively study the possible modulatory effects of A. vera and decipher the underlying mechanisms at play during the amelioration of chromium-induced toxicity. Such studies would warrant its use against managing heavy metal toxicity.

The onset and progression of hepatocellular carcinoma (HCC) is associated with several molecular and physiological changes in the tumor microenvironment. This provides a rationale for studying these changes throughout hepatic carcinogenesis and their possible modulation by putative anti-cancer agents. The present study was designed to look into the effects of lycopene enriched tomato extract (LycT) on markers linked with hypoxia, angiogenesis and metastasis at advanced stages of N-nitrosodiethylamine (NDEA) induced HCC in mice. Female balb/c mice were divided into four groups: Control, NDEA, LycT and LycT+NDEA. LycT was able to inhibit tumor formation and retard the development of histoarchitectural alterations which was consonance with the serum levels of alpha-feto protein. HCC development was associated with aggravated expression of markers linked to hypoxia (HIF), angiogenesis (VEGF, CD 31) and metastasis (MMP-2, MMP-9). LycT mediated inhibition in tumorigenesis was accompanied by decrease in expression of these markers. 99mTc-mebrofenin assay revealed diminished hepatic function in NDEA group which improved with LycT administration. These observations at late stages of HCC and those of the early stages reported previously, convincingly demonstrate that LycT effectively mitigated hepatic cancer possibly by modulating hypoxia, angiogenesis and metastasis.

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg⁻¹) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg⁻¹, orally, twice a day, PB 3 g kg⁻¹, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g⁻¹) as compared to PB (37.771 mg g⁻¹). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.

BACKGROUND: The present study aims to unravel the pro-apoptotic, anti-metastatic, and anti-telomerase activity of aqueous extract of Tinospora cordifolia stem (Aq.Tc) and its active component arabinogalactan (AG) during Benzo(a)pyrene [B(a)P]-induced lung tumorigenesis in mice. MATERIALS AND METHODS: Lung tumors were induced in male BALB/c mice using B(a)P as a carcinogen. Animals were administered twice with 50 mg/kg b.wt (i.p.) dosage of B(a)P at the 2^nd and 4^th week of the study. Mice were orally treated with Aq.Tc and AG on alternate days at a dose of 200 mg/kg b.wt and 7.5 mg/kg b.wt, respectively, for continuous 22 weeks. RESULTS: Oral administration of animals with Aq.Tc and AG suppressed the development of lung carcinogenesis by modulating the mRNA and protein expressions of different apoptotic genes; bcl-2, bax, caspase 3, and caspase 9. The pro-apoptotic proficiency of Aq.Tc and AG was further confirmed by DNA agarose gel electrophoresis showing fragmentation in B(a)P + Aq.Tc group and smear formation in B(a)P + AG group. In contrast to the control group, an increase in tumor invasion factors such as matrix metalloproteinases-2 (MMP-2) and MMP-9 was also observed in B(a)P treated animals. Nevertheless, Aq.Tc and AG treatment effectively mitigated the B(a)P-induced upregulation of MMP-2 and MMP-9. The activity of the telomerase enzyme was also observed to be upregulated in B(a)P treated animals which consecutively found to get normalized with the parallel administration of Aq.Tc and AG. CONCLUSION: Aq.Tc and AG successfully mitigated the altered expression of apoptosis, metastasis, and telomerase activity-associated genes during pulmonary carcinogenesis.

Aim: The present study was carried out to determine the protective potential of Lycopene enriched tomato extract (LycT) against hepatic and renal damage caused in mice by dexamethasone administration. Study Design: Male LACA mice were randomly divided into four treatment groups (n=6-7 animals per group) depending upon the treatment they received. Group I (control) animals served as control and were orally administered with olive oil (vehicle) thrice a week for five weeks. Group II (DEX) animals were intraperitoneallly (i.p.) administered with dexamethasone at a dose of 5 mg/kg b.w. on alternate days for three weeks. Group III (LycT) animals were orally (p.o.) administered with LycT at a dose of 5 mg/kg b.w. on alternate days for five weeks. Group IV (LycT+DEX) animals were co-administered with LycT (p.o.) and dexamethasone (i.p.) according to the above mentioned dose regimen Results: Dexamethasone caused hepatic and renal damage as evident from disturbed histoarchitecture, deranged levels of organ function markers (alkaline phosphatase, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, total and direct bilirubin, urea, creatinine) and enhanced level of cell damage (lactate dehydrogenase) and oxidative stress (lipid peroxidation) markers. Increased blood glucose level, decreased hepatic glycogen level along with inhibited activities of enzymes involved in glycolysis (hexokinase, phosphoglucoisomerase) indicated altered glucose metabolism in DEX group. The mitigation in histoarchitectural alterations, cell damage and oxidative stress markers, improved levels of organ function markers, blood glucose level along with ramped up antioxidant defense system indicated the protective potential of LycT against dexamethasone induced ill effects. Conclusions: These results point towards beneficial effects of LycT against dexamethasone induced damage to hepatic and renal tissues in mice.