Trimethoprim-sulfamethoxazole increase micronuclei formation in peripheral blood from weanling well-nourished and malnourished rats

Abstract

The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is a widely used drug. In spite of this, there are few reports on its genotoxicity, and the results are controversial. Severe malnutrition is a complex condition that increases the susceptibility to infections. Consequently, drugs are extensively used in malnutrition cases. Experimental animal models have been widely used to study the effects of malnutrition. Neonatal rats were experimentally malnourished (UN) during lactation. The UN rats weighed 51.1% less than the well-nourished (WN) controls and had lower concentrations of serum protein and blood lipids. The micronucleus (MN) assay is useful for detecting chromosome damage induced by nutritional deficiencies. In vivo rodent MN assays have been widely used to screen genotoxic agents. In this study, we have evaluated the frequency of spontaneous and TMP-SMX-induced micronuclei in the peripheral blood of weanling (21 days of age) rats using a flow cytometric analysis technique. The spontaneous frequency of micronucleated reticulocytes (MN-RETs) was 2.7 times greater in the UN rats than in the WN rats. In rats that were not treated with TMP-SMX, the percentage of reticulocytes was significantly lower (41.1%) in the UN rats than the WN controls. A therapeutic dose of TMP-SMX (80 mg/kg (TMP), 400 mg/kg (SMX) for 48 hr) increased MN-RETs in the WN and in the UN rats. The data demonstrate the genotoxic effect of this drug. The results indicate that severe protein-calorie restriction and drug treatment enhance DNA damage in rat peripheral blood reticulocytes, potentially increasing the risk of negative effects on health.

Virgin coconut oil protects against liver damage in albino rats challenged with the anti-folate combination, trimethoprim-sulfamethoxazole

“…Earlier, rashes and gastrointestinal distress were believed to be the most frequent side effects of the drug until a reported case of hyperkalemia [4]. Furthermore, researchers have demonstrated the hepatotoxic, nephrotoxic, and genotoxic effects of the antibiotic [5][6][7].…”

Chromosomal Disturbances during Mitotic Activity of Root Tip Cells in Allium by Certain Commonly Used Antibiotics

“…50 Cyto-genotoxicity of the combination (Sulfamethoxazole + trimethoprim) such as micronucleus and DNA damage was reported in rats. 51 The micronuclei formation was observed in nourished and malnourished rats after treatment with Trimethoprim + sulfamethoxazole. The antimalarial compound artesunate showed genotoxicity and cytotoxicity in the somatic cells of mice and human lymphocytes.…”

Efecto genotóxico y mutagénico de la desnutrición moderada y grave en reticulocitos y eritrocitos de rata

“…Body weight groups were compared using T-tests and Dunnett's multiple-comparisons test with GraphPad Software version 6.0 (San Diego, CA, USA). MFs (RET CD59− and RBC CD59− frequencies) are expressed per 10 6 RETs or total RBCs, and the data were log (10) transformed. The incidence of RETs is expressed as the frequency percentage.…”

“…These procedures include measurements of DNA-associated proteins and gene-specific mutations (i.e., heritable alterations in the DNA sequence) [5]. Studies have detected increased genetic damage in malnourished humans and animal models, as measured based on sister chromatid exchange, chromosomal aberrations, DNA damage determined through single-cell electrophoresis (i.e., comet assay), and the percentage of peripheral blood reticulocytes (RETs) with micronuclei [9][10][11][12]. For instance, we have observed significant increases in the micronucleus (MN) frequency in RETs from the peripheral blood of malnourished (UN) rats compared with wellnourished (WN) rats [10].…”

“…Studies have detected increased genetic damage in malnourished humans and animal models, as measured based on sister chromatid exchange, chromosomal aberrations, DNA damage determined through single-cell electrophoresis (i.e., comet assay), and the percentage of peripheral blood reticulocytes (RETs) with micronuclei [9][10][11][12]. For instance, we have observed significant increases in the micronucleus (MN) frequency in RETs from the peripheral blood of malnourished (UN) rats compared with wellnourished (WN) rats [10]. Increases in DNA damage have also been detected in the peripheral blood lymphocytes of malnourished children [13][14][15].…”