EFVb-HAART Increases Mortality, Locomotor Deficits and Reduces Reproductive Capacity in Drosophila melanogaster

Iorjiim, Walter Mdekera; Omale, Simeon; Etuh, Monday Alexander; Bagu, Great David; Ogwu, Sunshine Ochala; Gyang, Steven Samuel

doi:10.9734/jabb/2020/v23i130136

Cited by 11 publications

(22 citation statements)

References 25 publications

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“…Nevertheless, HAART induces oxidative stress [2,3,4] and life expectancy in HAART treated HIV patients is shorter than the uninfected population [3]. Recently, Iorjiim et al [5] reported that D. melanogaster exposed to EFV b -HAART developed locomotor deficits, decreased lifespan as well as reproductive capacity, and hypothesized that these observations might partly be oxidative stress-related toxicities. Therefore, this study aims to evaluate the toxicological impact of EFV b -HAART on total protein, some antioxidants parameters (total thiols, Glutathione-S-transferase (GST), Catalase (CAT), Superoxide dismutase (SOD) and Malondialdehyde (MDA) levels (as a measure of free radical generation) in D. melanogaster.…”

Section: Introductionmentioning

confidence: 99%

Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

Iorjiim

Omale

Bagu

et al. 2020

JAMPS

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Objective: This study intended to evaluate the toxic effects of Efavirenz-based highly active antiretroviral therapy (EFVb-HAART) on some antioxidant parameters, and free radical generation in D. melanogaster. Materials and Methods: The study was carried out at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019. Sixty (60) D. melanogaster (both sexes) 1-4 days old were exposed by ingestion to graded concentrations of EFVb-HAART (93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg) or 1000 mL distilled water (control) each per 10 g fly food for five days. All concentrations were diluted with 1000 mL distilled water and incorporated in cold fly food in five replicates. Treated flies were anesthetized under ice, homogenized, centrifuged, and the supernatant used to assay for Total protein, Total thiol, Glutathione-S-transferase, Catalase, Superoxide dismutase, and Malondialdehyde levels. Statistical significance was accepted at P< 0.05. Results: The result showed significantly (P<0.05) increased total protein (1.05±0.0 - 1.34±0.12 Vs. 0.56±0.14 mg/ml) and Malondialdehyde levels (1.63±0.20 – 3.72±0.53 Vs. 0.79±0.10 units/mg protein) in all tested groups versus unexposed. Conversely, Total thiol content (1.96±0.33-0.38±0.10 Vs. 5.31±0.31 units/mg protein) Glutathione-S-transferase (2.20±0.30-1.01±0.27 Vs. 4.31±0.24 units/mg protein), Catalase (171.70±50.13-104.34±9.56 Vs. 368.00±7.56 units/mg protein) and Superoxide dismutase (3.18±0.29-1.44±23 Vs. 5.34±1.35 units/mg protein) activities all decreased significantly (P<0.05) as concentrations increased in all test groups versus unexposed. Conclusion: Overall, our results suggest that the mechanism of EFVb-HAART toxicity involves sterile immune response observed as increased protein contents, oxidative stress evidenced by depleted oxidative stress-antioxidant parameters, and possible free radical generation shown by increased malondialdehyde levels. Human-based studies are required for deeper understanding of these EFVb-HAART toxicities.

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Section: Introductionmentioning

confidence: 99%

Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

Iorjiim

Omale

Bagu

et al. 2020

JAMPS

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“…Colpo et al [35] observed similar findings in Drosophila treated with Ilex paraquariensis post feed on high-fat diet. The choice of 7 days treatment period was appropriate as greater than 95 % of the fly population were alive on the seventh day [36].…”

Section: Discussionmentioning

confidence: 99%

Fruiting Body of Pleurotus Ostreatus Reduces Serum Glucose and Modifies Oxidative Stress in Type 2 Diabetic: Drosophila Melanogaster (Fruit-Fly)

Omale¹,

Aguiyi²,

Bukar³

et al. 2020

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Mushrooms, which possess medicinal properties, are also considered a good source of food and basic nutrients. Diabetic patients now use edible mushrooms as a source of low-calorie food. Mushrooms are used to treat and prevent diseases such as diabetes, obesity, heart disease, hyperacidity, cancer, hypertension and also act as immune modulators. In this study, the antidiabetic and antioxidant effects of the fruiting body of Pleurotus ostreatus (PO) in sucrose-induced type-2 diabetic Drosophila melanogaster was investigated. The fresh fruiting body of PO was obtained from the mushroom farm of the Africa Centre of Excellence in Phytomedicine Research and Development (ACEPRD) and dried with the aid of the ASPRE dryer. The aqueous extract of the dried powder was used for the anti-diabetic and survival assay. The fly homogenate was evaluated for circulating glucose, total thiol, acetylcholinesterase, catalase and glutathione-S-transferase. PO was observed to prolong D. melanogaster's survival time as more flies (> 50%) survived on the extract compared to control (47%), after 28 days. There was a significant (P < 0.05) decrease in the circulating glucose of the treated flies compared with those that were untreated; while no statistical (P > 0.05) difference was observed between the metformin and PO treated groups. In the antioxidant study, an insignificant (P > 0.05) difference between the untreated and treated groups was observed. Catalase activity showed a significant (P < 0.05) difference between the diabetic untreated and PO treated groups. We conclude that the fruiting body of P. ostreatus possessed potent hypoglycemic activities in D. melanogaster induced type-2 diabetes, possibly linked to its antioxidant property.

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“…The D. melanogaster (Harwich strain) was sourced at the ACEPRD, University of Jos. The fly stock was inbred and maintained at standard environmental conditions, as previously described [20]. The flies were fed on Drosophila food composed of yellow cornmeal (100 g), brewer's yeast (20 g), agar (16 g), and the preservative methylparaben (1 g) [25].…”

Section: Animal Modelmentioning

confidence: 99%

“…HAART drug-related ADRs include nausea, vomiting, and skin eruptions [4]. Other severe ADRs associated with HAART include induction of free radicals (reactive oxygen and nitrogen species, RONS) [18,19], reduced reproductive capacity [1,20], neurodegenerative diseases [21], and accelerated aging [22].…”

Section: Introductionmentioning

confidence: 99%

“…The reproductive and oxidative stress toxicities particularly are of serious clinical concern. Briefly, the majority of people on antiretroviral therapies are of childbearing age [9], and HAART drugs are known culprits in reproductive druginduced anomalies [20] and oxidative stress induction [1,3,9]. The literature is replete of the fact that over 75 % of genes implicated in aging, functional senescence, and human diseases are conserved in D. melanogaster [23].…”

Section: Introductionmentioning

confidence: 99%

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Reproductive and Oxidative Stress Toxicity of Dolutegravir-Based Combination Antiretroviral Therapy in Drosophila melanogaster

Iorjiim

Omale

Bagu

et al. 2020

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Background/Objective: Dolutegravir-based highly active antiretroviral therapy (DTG-HAART) is the preferred regimen in the management of HIV/AIDS. However, the reproductive and oxidative stress toxicity of DTG-HAART is unknown. This study was designed to investigate the reproductive and oxidative stress toxicity of DTG-HAART in Drosophila melanogaster. Materials and Methods: We performed all the experiments at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019. D. melanogaster, (1-4 days old), were fed with ten different concentrations of DTG-HAART (range 15 mg -595 mg) or 1000 mL distilled water per 10 g food for seven days to calculate the LD50, then treated with 93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg or 1000 µL distilled water each per 10 g fly food for five days in five replicates. Subsequently, longevity, fly fecundity, and negative geotaxis evaluated. Also, activities of Acetylcholinesterase, Glutathione-S-transferase, Superoxide dismutase, Catalase, as well as Total thiol, and Malondialdehyde levels were investigated in the whole fly homogenate. Statistical values at P<0.05 were considered significant. Results: The LD50 of DTG-HAART in D. melanogaster was 106.4 mg. The result showed significantly decrease (P<0.001) in mean lifespan, fly emergence, Total thiol content, Acetylcholinesterase, Glutathione-S-transferase, Catalase, and Superoxide dismutase activities in the exposed groups compared to the unexposed. Inversely, the Malondialdehyde level in the test groups was significantly (P<0.001) elevated compared to unexposed. Conclusion: Collectively, our results suggest that DTG-HAART toxicity was associated with reproductive deficits and oxidative stress induction in D. melanogaster, here observed as reduced fly fecundity, mean lifespan, AChE activity, antioxidant parameters, and elevated MDA level. This study, thus, raised concerns for long term use of DTG-HAART by HIV patients.

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EFVb-HAART Increases Mortality, Locomotor Deficits and Reduces Reproductive Capacity in Drosophila melanogaster

Cited by 11 publications

References 25 publications

Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

Fruiting Body of Pleurotus Ostreatus Reduces Serum Glucose and Modifies Oxidative Stress in Type 2 Diabetic: Drosophila Melanogaster (Fruit-Fly)

Reproductive and Oxidative Stress Toxicity of Dolutegravir-Based Combination Antiretroviral Therapy in Drosophila melanogaster

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