Cotrimoxazole and Folate Metabolism

Bateson, M. C.; Hayes, James; Pendharkar, P

doi:10.1016/s0140-6736(76)92593-9

Cited by 14 publications

(3 citation statements)

References 29 publications

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“…The association of T M P and S M Z in fixed proportions is widely used for prophylaxis and/or treatment of pneumocistis carinii and/or bacterial infections in oncology patients. Although that association has been claimed to have no effect on folate metabolism in man (Frisch, 1973;Bateson et al, 1976) many publications have described megaloblastic changes of blood elements suggestive of folate deficiency (Herbert, 1973;Koutts et al, 1973;Jenkins et al, 1970). Recent work done by Golde et nl(1978) has demonstrated that TMP, at clinically relevant concentration, can inhibit human and murine erythropoiesis and granulopoiesis in vitro.…”

Section: Discussionmentioning

confidence: 99%

Effects of Trimethoprim on Leukaemic Cells in Vitro

Rivard

Momparler

1981

Br J Haematol

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Trimethoprim-Sulfamethoxazole (TMP-SMZ) is a fixed combination of antibiotics which is widely used for prophylaxis and treatment of infections in patients undergoing cancer chemotherapy. TMP has been reported to inhibit growth of haemopoietic stem cells in vitro. If TMP-SMZ inhibits leukaemic cell growth, it could interfere with antileukaemic treatment, especially with S phase specific agents. TMP-SMZ at a concentration of 10 micrograms/ml (TMP) produced 50% inhibition of incorporation of 3H-deoxyuridine in DNA of L1210 and human lymphoblastic leukaemia cell. TMP-SMZ (1 g/ml TMP) produced 30% prolongation of doubling time of L1210 in vitro. Pure TMP (10 micrograms/ml) but not SMZ (50 micrograms/ml) produced the same effect as TMP-SMZ. Cell inhibitory effects could be completely reversed by folinic acid. These findings suggest that TMP produces some degree of inhibition of dihydrofolic acid reductase in mammalian cells and can potentially influence the effects of chemotherapy on tumour and/or host cells.

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Section: Discussionmentioning

confidence: 99%

Effects of Trimethoprim on Leukaemic Cells in Vitro

Rivard

Momparler

1981

Br J Haematol

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“…However, these increases were not equal to WM indicating antibiotic treatments along will not be able to achieve the fitness of TM to the level of WM. On the other hand, the larval life span of cotrimoxazole antibiotic-treated TM mosquitoes showed a significant increase compared to the other two antibiotictreated samples (Figure 4(c), Kruskal-Wallis test followed by Dunn's test, p < 0:05) suggesting the folate deficiency that caused by co-trimoxazole in folate synthesis pathway prolongs the life span of larvae [31][32][33]. Further, the effect of antibiotic on mating competitiveness showed a significant increase in the TM progeny percentage of field release scenario mix (Table 3, chi-square test, p < 0:05) of the laboratory trials.…”

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confidence: 89%

Assessment of Developmental and Reproductive Fitness of Dengue-Resistant Transgenic Aedes aegypti and Improvement of Fitness Using Antibiotics

Ramyasoma

Gunawardene

Hapugoda

et al. 2021

BioMed Research International

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Background. Genetic modification offers opportunities to introduce artificially created molecular defence mechanisms to vector mosquitoes to counter diseases causing pathogens such as the dengue virus, malaria parasite, and Zika virus. RNA interference is such a molecular defence mechanism that could be used for this purpose to block the transmission of pathogens among human and animal populations. In our previous study, we engineered a dengue-resistant transgenic Ae. aegypti using RNAi to turn off the expression of dengue virus serotype genomes to reduce virus transmission, requiring assessment of the fitness of this mosquito with respect to its wild counterpart in the laboratory and semifield conditions. Method. Developmental and reproductive fitness parameters of TM and WM have assessed under the Arthropod Containment Level 2 conditions, and the antibiotic treatment assays were conducted using co-trimoxazole, amoxicillin, and doxycycline to assess the developmental and reproductive fitness parameters. Results. A significant reduction of developmental and reproductive fitness parameters was observed in transgenic mosquito compared to wild mosquitoes. However, it was seen in laboratory-scale studies that the fitness of this mosquito has improved significantly in the presence of antibiotics such as co-trimoxazole, amoxicillin, and doxycycline in their feed. Conclusion. Our data indicate that the transgenic mosquito produced had a reduction of the fitness parameters and it may lead to a subsequent reduction of transgenic vector density over the generations in field applications. However, antibiotics of co-trimoxazole, amoxicillin, and doxycycline have shown the improvement of fitness parameters indicating the usefulness in field release of transgenic mosquitoes.

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“…Numerous cases of trimethoprim-sulfamethoxazole-induced megaloblastic arrest have been reported; many of these occurred in patients with preexisting folate or BI2 deficiency (5,6). While the effect of trimethoprim-sulfamethoxazole on folate metabolism and hematopoiesis in humans has been disputed (7), the results of an in vitro study suggested that trimethoprim and sulfamethoxazole may inhibit erythroid and granulocyte colony-forming units at concentrations achieved at therapeutic doses, and that this inhibition was reversed by folinic acid (8).…”

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confidence: 99%