Role of Vitamin D and Its Analogues in Diabetic Nephropathy: A Meta-analysis.

BACKGROUND: Diabetic nephropathy remains one of the most common causes of chronic kidney disease in the United States and is associated with significant morbidity and mortality. Recently, there have been emerging data highlighting the role of vitamin D and its analogue in chronic kidney disease especially diabetic nephropathy independent of its effect on bone metabolism. METHODS: This study aimed to evaluate effect of supplementing vitamin D and its analogues on halting or slowing progression of diabetic nephropathy. Electronic databases (PubMed, Scopus, Google scholar) were searched and randomized controlled trials (RCTs) that investigated the use of vitamin D and its analogs for diabetic nephropathy were studied. This meta-analysis of RCTs performed in accordance with Preferred Reporting Items for Systematic review and Meta-analysis statement. RESULTS: This meta-analysis included 9 RCTs and suggested a favorable trend with respect to an effect of vitamin D and its analogues on albuminuria though this did not reach statistical significance (MD, -0.17; 95% CI, -0.34-0.01; P = 0.06]. Serum calcium was unaffected suggesting safe use of these agents. CONCLUSIONS: Use of vitamin D and its analogues may have potential as an adjuvant therapy for reducing albuminuria and slowing progression of diabetic nephropathy but further studies are needed.

Ameliorative Effect of Green Tea Catechin Against Cadmium Chloride-Induced Testicular Toxicity in Mice.

The present study was designed to evaluate the effect of green tea catechin (7500 µg/kg/animal/day) against cadmium-induced testicular dysfunctions and oxidative stress in the testes of mice. For this purpose, Swiss albino mice were divided into six groups: group I, negative control; group II, catechin-treated control; group III, cadmium chloride (CdCl2)-treated control; group IV, experimental group I; group V, experimental group II; and group VI, experimental group III. Animals from all of these groups were necropsied at various post-treatment intervals between 12 hours and 30 days for various biochemical alterations in the testes. CdCl2 intoxication resulted in a significant decline in testicular total proteins, cholesterol, and alkaline phosphatase, whereas acid phosphatase and lipid peroxidation exhibited a noticeable augmentation as compared to negative control. Catechin treatment effectively protected CdCl2-induced alterations in all such parameters throughout the experiment. Catechin was effective in reducing the CdCl2-induced augmentation of phase I (P450 and CYPB5) as well as phase II (DT-diaphorase and glutathione-S-transferase) enzymes in testes. Furthermore, CdCl2 intoxication was found to attenuate the antioxidant potential of testes, which was however augmented when supplemented with green tea extract. Compared to CdCl2-treated control mice, superoxide dismutase, glutathione peroxidase, glutathione, and catalase levels were significantly decreased in testes. Indeed, green tea catechin significantly increased testicular antioxidant enzymatic activities compared to those given CdCl2 alone. In conclusion, the use of green tea extract appeared to be beneficial to a great extent in inhibiting and restoring the testicular injuries induced by CdCl2 intoxication in mammals.

Amelioration of chemical-induced skin carcinogenesis by Aegle marmelos, an Indian medicinal plant, fruit extract.

Chemoprevention is a novel approach to study the anti-initiating and anti-tumor-promoting efficacy of medicinal plants and their active principles. The present study investigated the chemopreventive potential of Aegle marmelos fruit extract in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis and its influence on oxidative stress and the antioxidant defense system. The oral administration of A marmelos at 100 mg/kg body weight/day during peri-initiational, postinitiational, and peri- & postinitiational phases of papillomagenesis showed significant reduction in tumor incidence, tumor yield, tumor burden, and cumulative number of papillomas when compared with carcinogen-treated control. The average latent period significantly increased (7.88 weeks; control group) to 9.45, 11.11, and 11.54 weeks in different A marmelos extract (AME) experimental groups. Enzyme analysis of skin and liver showed a significant elevation in antioxidant parameters such as superoxide dismutase, catalase, glutathione, and vitamin C in AME-treated groups when compared with the carcinogen-treated control. The elevated level of lipid peroxidation in the positive control was significantly inhibited by AME administration. These results indicate that AME has the potential to reduce chemical-induced skin papillomas by enhancing the antioxidant defense system.

Chemically induced skin carcinogenesis in mice and its prevention by Aegle marmelos (an Indian medicinal plant) fruit extract.

This study assessed the chemopreventive potential of the Aegle marmelos plant on mouse skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by croton oil. A significant reduction in tumor incidence, tumor burden, tumor multiplicity, and the cumulative number of papillomas, along with a significant increase in the average latent period, was recorded in mice treated orally with A. marmelos extract (AME) at peri - and post-initiation phases (i.e., 7 days before DMBA application and continued until the end of the experiment) of papillomagenesis as compared with the carcinogen-treated controls. Furthermore, a significant increase in catalase activity, reduced glutathione and total proteins, and a depleted level of lipid peroxidation were observed in liver and skin of AME-treated animals as compared with the carcinogen-treated controls. Thus, the oral administration of AME, at a dose of 50 mg/kg body wt per day per animal, was found to be significantly effective in reducing skin tumors against chemical carcinogenesis in mice.

Modulatory influence of Phyllanthus niruri on oxidative stress, antioxidant defense and chemically induced skin tumors.

The present study evaluates the modulatory potential of Phyllanthus niruri on chemically induced skin carcinogenesis, and its influence on oxidative stress and the antioxidant defense system. Oral administration of P. niruri extract (PNE), during peri- (Gr. III), post- (Gr. IV), or peri- and post- (Gr. V) initiational stages of 7,12-dimethylbenz(a) anthracene (DMBA)-croton oil­induced papillomagenesis considerably reduced tumor burden to 4.20, 4.00, and 3.33(positive control value 6.20); cumulative number of papillomas to 21, 16, and 10, respectively, (positive control value 62); and incidence of mice bearing papillomas to 50, 40, and 30%, respectively (positive control value 100%), but significantly increased the average latent period to 10.14, 10.62, and 11.60, and inhibition of tumor multiplicity to 66, 74,and 83%, respectively. Enzyme analysis of skin and liver showed a significant (p ≤ 0.05, ≤ 0.01, ≤ 0.001) elevation in antioxidant parameters such as superoxide dismutase, catalase, glutathione, and vitamin C in PNE-treated groups (Gr. III­V) when compared with the carcinogen-treated control (Gr. II). The elevated level of lipid peroxidation in the carcinogen-treated positive control group was significantly (p ≤ 0.05, ≤ 0.01, ≤ 0.001) inhibited by PNE administration. These results indicate that P. niruri extract has potentiality to reduce skin papillomas by enhancing antioxidant defense system.

Elimination of deleterious effects of DMBA-induced skin carcinogenesis in mice by Syzygium cumini seed extract.

The inhibition of tumor incidence by hydro-alcoholic extract of S.cumini seed was evaluated in mice on two stage process of skin carcinogenesis induced by single application of 7, 12-dimethyl benz(a)anthracene (100 µg/100µl of acetone), and 2 weeks later promoted by repeated application of croton oil (1% acetone/thrice in a week) till the end of the experiment (i.e. 16 weeks). Oral administration of extract at a dose of 250mg/kg b.wt./day at the peri-initiational stage (i.e. 7 days before and 7 days after DMBA application), promotional stage (i.e. from the time of croton oil application) and at both the stages (i.e. 7 days prior to DMBA application & continued till the end of experiment) to the mice, recorded a significant reduction in tumor incidence to 37.5, 50 & 25% respectively in comparison to the carcinogen treated control, where tumor incidence was found as 100%. Tumor yield and Tumor burden were also significantly reduced by SCE. Similarly, the cumulative number of papillomas after 16 weeks was 68 in the control group, which was reduced to 15, 21 & 8 in the animals treated with the SCE continuously at peri-, post- and peri- & post- initiation stage respectively. A significant impairment was noticed in the levels of reduced glutathione, superoxide dismutase, catalase & protein and enhancement in LPO in liver and skin of carcinogen treated control mice as compared with vehicle treated mice. All such parameters were returned to near normal value by administration of SCE to DMBA treated mice. These results suggest a possible chemopreventive property of S.cumini against DMBA induced skin carcinogenesis in mice.

Protective effect of Alstonia scholaris against radiation-induced clastogenic and biochemical alterations in mice.

We studied the radioprotective effect of Alstonia scholaris bark extract (ASE) on cytogenetic alterations in the form of chromosomal aberrations and micronuclei induction in bone marrow. For this purpose, one group of male Swiss albino mice was exposed to 2.5 Gy gamma radiation to serve as the irradiated control, while the other group received ASE (100 mg/kg bwt/d) orally for 5 consecutive days 30 min before irradiation to serve as the experimental group. Results indicated that dicentrics and chromosomal exchanges were increased at 12 h post-exposure in both groups, followed by a gradual decline and then disappearance by d 15 and 7, respectively. However, the occurrence of chromatid breaks and acentric fragments was also maximum at 12 h, and later decreased without attaining the normal value, even up to the last necropsy interval. The percentage of such aberrations was significantly less in the ASE-pretreated irradiated animals. The incidence of chromosome breaks and centric rings kept increasing up to d 1, but then declined gradually and reached zero beginning at d 7; they were significantly lower in the ASE-treated irradiated group at the early intervals. A significant decrease in glutathione (GSH) and an increase in lipid peroxidation were observed after radiation exposure in untreated controls, whereas ASE-pretreated irradiated animals exhibited a significant increase in GSH and a decrease in lipid peroxidation; however, the values remained below normal. The results from the present study suggest that ASE pretreatment provides protection against radiation-induced chromosomal damage and micronuclei induction in the bone marrow of mice.

Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.

Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several isozymes of superoxide dismutase; the minerals selenium and zinc; and polysaccharides in aloe vera.

Influence of Rosemarinus officinalis extract on radiation-induced intestinal injury in mice.

The radioprotective effect of Rosemarinus officinalis extract (ROE) was studied in mice exposed to 3 Gy gamma radiation. Crypt survival, villus length, apoptotic cells, mitotic figures and goblet cells in intestine were studied at different autopsy intervals i.e. 12 hrs to 30 days after irradiation. Maximum changes in all the intestinal parameters were observed on day 3 after irradiation. Irradiated animals with ROE pretreatment exhibited a significant increase in the number of crypt cells, mitotic figures and villus length; whereas a significant decrease in the counts of apoptotic and goblet cells showed a significant decrease respective controls at all the autopsy intervals. Irradiation of animals resulted an elevation in lipid peroxidation and a reduction in glutathione concentration in the intestine at 1 hour post-irradiation. In contrast, ROE treatment before irradiation caused a significant depletion in lipid peroxidation and elevation in glutathione levels.

Anticancer activity of an Indian medicinal plant, Alstonia scholaris, on skin carcinogenesis in mice.

Alstonia scholaris, commonly known as sapthaparna, has been used for centuries in Ayurvedic medicine for treatment of various disorders. The objective of this study was to investigate the possible chemopreventive and anti-oxidative properties of this medicinal plant on two-stage process of skin carcinogenesis induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 lg/100 ll acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks) in Swiss albino mice.The tumor incidence, tumor yield, tumor burden and cumulative number of papillomas were found to be higher in the carcinogen treated control (without ASE treatment) as compared to experimental animals (ASE treated). Furthermore, a significant increase in reduced glutathione, superoxide dismutase and catalase but decrease in lipid peroxidation was measured in ASE administered experimental groups than the carcinogen treated control. The present study demonstrates the chemopreventive potential of Alstonia scholaris bark extract in DMBA-induced skin tumorigenesis in Swiss albino mice.