Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.; Essop, M. Faadiel

doi:10.1371/journal.pone.0170344

Cited by 10 publications

(5 citation statements)

References 48 publications

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“…RE co-treatment was also reported to attenuate the effects of several other drugs. For example, RE can attenuate the effects of Human immunodeficiency virus (HIV) protease inhibitors [146], and it can interact with 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors [147], anti-arrhythmic agents [148], calcium channel agonists [149], antihistamines [150], and immunosuppressants [151].…”

Section: Resveratrol Interacts With and Attenuates The Action Of Othementioning

confidence: 99%

Potential Adverse Effects of Resveratrol: A Literature Review

Shaito

Posadino

Younes

et al. 2020

IJMS

395

293

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Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects.In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.

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Section: Resveratrol Interacts With and Attenuates The Action Of Othementioning

confidence: 99%

Potential Adverse Effects of Resveratrol: A Literature Review

Shaito

Posadino

Younes

et al. 2020

IJMS

395

293

View full text Add to dashboard Cite

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“…Then, a RESV cotreatment, provided that suitable plasma concentrations are reached (Calvo-Castro et al, 2018), may help to overcome the side effects. Of note, RESV was reported to attenuate the effects of PIs on rat body weight while improving the cardiac parameters (Symington, Mapanga, Norton, & Essop, 2017). A putative role of UCP1 may account in part for these observations although no information regarding its expression is provided.…”

Section: Resveratrol Partially Reversed Lpv's Effect On Ucp1 Expressionmentioning

confidence: 99%

Resveratrol and HIV‐protease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes

Ravaud

Paré

Yao

et al. 2019

Journal Cellular Physiology

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Brown and brown-like adipocytes (BBAs) control thermogenesis and are detected in adult humans. They express UCP1, which transforms energy into heat. They appear as promising cells to fight obesity. Deciphering the molecular mechanisms leading to the browning of human white adipocytes or the whitening of BBAs represents a goal to properly and safely control the pathways involved in these processes.Here, we analyzed how drugs endowed with therapeutic potential affect the differentiation of human adipose progenitor-cells into BBAs and/or their phenotype. We showed that HIV-protease inhibitors (PI) reduced UCP1 expression in BBAs modifying their metabolic profile and the mitochondria functionality.Lopinavir (LPV) was more potent than darunavir (DRV), a last PI generation. PPARγ and PGC-1α were decreased in a PI or cell-specific manner, thus altering UCP1's constitutive expression.In addition, LPV altered p38 MAPK phosphorylation, blunting then the β-adrenergic responses. In contrast, low doses of resveratrol stimulated the activatable expression of UCP1 in a p38 MAPK-dependent manner and counteracted the LPV induced loss of UCP1. This effect was independent of the resveratrol-induced sirtuin-1 expression.Altogether our results uncover how drugs impact crucial components of the networks regulating the expression of the thermogenic signature. They provide important information to control the relevant pathways involved in energy expenditure. K E Y W O R D Sadipose tissue, aging, brown adipocytes, energy metabolism, HIV protease inhibitors, p38 mitogen-activated kinase, resveratrol, sirtuin-1, UCP1, white adipocytes

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“…Nevertheless, nor RSV or RSVO was able to prevent this alteration in our experimental model. A pilot study demonstrated that a 4-month protocol of treatment with RSV prevented the body weight loss elicited by anti-HIV protease inhibitors in rats [49]. It is tempting to suggest that a long-term of treatment with RSVO might prevent CFA-related body weight reduction.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation

et al. 2019

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This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenaninduced acute edema, complete Freund's adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10-15 mg/kg) or RSV (100-200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group-46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the proinflammatory cytokine interleukin-6 (IL-6), associated with an increase of the antiinflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This

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Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

Cited by 10 publications

References 48 publications

Potential Adverse Effects of Resveratrol: A Literature Review

Potential Adverse Effects of Resveratrol: A Literature Review

Resveratrol and HIV‐protease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes

Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation

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