A comparison of vitamin A and leucovorin for the prevention of methotrexate-induced micronuclei production in rat bone marrow

INTRODUCTION: Methotrexate, a folate antagonist, is a mainstay treatment for childhood acute lymphoblastic leukemia. It is also widely used in a low dose formulation to treat patients with rheumatoid arthritis. In rats, methotrexate is known to induce micronuclei formation, leading to genetic damage, while vitamin A is known to protect against such methotrexate-induced genetic damage. Leucovorin (folinic acid) is generally administered with methotrexate to decrease methotrexate-induced toxicity. OBJECTIVES: We aimed to determine whether vitamin A and leucovorin differed in their capacity to prevent formation of methotrexate-induced micronuclei in rat bone marrow erythrocytes. The present study also aimed to evaluate the effect of combined treatment with vitamin A and leucovorin on the formation of methotrexate-induced micronuclei. METHODS: Male and female Wistar rats (n=8) were injected with 20 mg/kg methotrexate (single i.p. dose). The control group received an equal volume of distilled water. The third and fourth groups of rats received vitamin A (5000 IU daily dose for 4 successive days) and leucovorin (0.5 mg/kg i.p. dose for 4 successive days), respectively. The fifth and sixth groups of rats received a combination of vitamin A and a single dose of methotrexate and a combination of leucovorin and methotrexate, respectively. The last group of rats received a combination of leucovorin, vitamin A and single dose of methotrexate. Samples were collected at 24 hours after the last dose of the treatment into 5 percent bovine albumin. Smears were obtained and stained with May-Grunwald and Giemsa. One thousand polychromatic erythrocytes were counted per animal for the presence of micronuclei and the percentage of polychromatic erythrocyte was determined. RESULTS: Comparison of methotrexate-treated rats with the control group showed a significant increase in the percentage of cells with micronuclei and a significant decrease polychromatic...

Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer: an indian experience.

BACKGROUND: Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55. The aim of t he present study was to analyze areduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage. MATERIAL AND METHODS: Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups. RESULTS: Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003), sensory neuropathy (p = 0.032) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01). CONCLUSION: Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity.

Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and antimutagenicity of Thunbergia laurifolia Linn.

Thunbergia laurifolia Linn has been reputed to have antitoxic effects for all toxic substances. In this present study, we evaluated its effect against the mutagenicity induced by aqueous extracts from Pueraria mirifica Airy Shaw & Suvatabundhu in male rats. The formation of micronuclei in polychromatic erythrocytes was induced by oral administration of an aqueous extract of P. mirifica at the doses of 400, 600, and 800 mg/kg to the rats for 30 days. The results were that the extracts of P. mirifica at doses of 600 and 800 mg/kg acted as a mutagenic agent by inducing higher frequencies of micronuclei as compared to the controls. For the antimutagenic test, P. mirifica extract at a dose of 600 mg/kg (minimal effective dose) was mixed with fresh and dried extracts of T. laurifolia in proportions of 7:3 and 1:1, respectively. The results of 4-week-treatment indicated that aqueous extracts of T. laurifolia, prepared by both fresh and dry methods, could significantly inhibit the induction of micronuclei as induced by P. mirifica. It could be concluded from the results that, under certain circumstances, T. laurifolia exhibits a significant antimutagenic activity. The use of P. mirifica and T. laurifolia as fusion herbal medicines is suggested.