Toxicological evaluation of an olive extract, H35: Subchronic toxicity in the rat

Heilman, Jacqueline M.; Anyangwe, Njwen; Tran, Nga; Edwards, James M.; Beilstein, Paul; López, José A.

doi:10.1016/j.fct.2015.07.007

Cited by 15 publications

(20 citation statements)

References 32 publications

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“…In addition, subchronic toxicity was evaluated at doses of 1000, 1500, and 2000 mg of hydoxytyrosol/kg, concluding no significant changes associated with the VOO extract compounds. Other authors have reported nosignificant toxic effects after a 90-days subchronic toxicity test of an extract with 35% of hydroxytyrosol, at doses of 125, 250, and 500 mg of hydroxytyrosol/kg/day [22,23], even though the last study reported a decrease in body weight and an increase in relative weight of liver, thymus, kidneys, and spleen in male rats. In addition, Kirkland et al evaluated the acute toxicity of a hydroxytyrosol-enriched extract (40%) and determined that 2000 mg of hydroxytyrosol/kg was well tolerated.…”

Section: Discussionmentioning

confidence: 99%

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract

et al. 2019

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The objective of this study was to determine the acute (one single dose), subacute (14 days), and sub-chronic (90 days) toxicity of an aqueous virgin olive oil (VOO) extract rich in hydroxytyrosol in rats. For acute/subacute toxicity, rats were divided into three groups. The control group received distilled water (n = 9), another experimental group received a single dose of 300 mg/kg (n = 3), and a third group received one dose of 2000 mg/kg (n = 4) during 14 days. The sub-chronic study included 60rats distributed in three groups (n = 20: 10 males and 10 females) receiving daily different three doses of the VOO extract in the drinking water during 90 days: (1) 100 mg/kg, (2) 300 mg/kg, and (3) 1000 mg/kg. In parallel, a fourth additional group (n = 20: 10 males and 10 females) did not receive any extract (control group). Clinical signs, body weight, functional observations of sensory and motor reactivity, hematological and biochemical analyses, and macroscopic and microscopic histopathology were evaluated. No adverse effects were observed after the administration of the different doses of the hydroxytyrosol-rich VOO extract, which suggests that the enrichment of VOO in its phenolic compound is safe, and can be used as functional foods for the treatment of chronic degenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract

et al. 2019

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“…This effect may be related to changes in the systemic redox environment, as the 300 mg/kg/d dosage increases plasma HPx levels. All the supplemented groups (i.e., exercised and sedentary) showed similar weight gain, suggesting no evidence for potential toxicity for the doses used [ 28 ]. However, the lower levels of HGB together with the higher HPx levels reported in the EXE300 group should be further studied as they may reflect a harmful effect of the higher HT dose when combined with exercise.…”

Section: Discussionmentioning

confidence: 99%

“…Since HT dosages up to 300 mg/kg/d are known to be safe for rodents [ 28 ], and a dosage of 20 mg/kg/d is known to exert an antioxidant effect [ 20 , 21 ], we hypothesized that the consumption of a low (20 mg/kg/d) dosage of HT during endurance exercise would induce an antioxidant effect, while a high (300 mg/kg/d) dosage would reverse this effect by inducing systemic oxidative stress. Our purpose was to describe the effects of a low and high HT dose for 10 weeks on the physical capacity and redox state of both sedentary and exercised rats.…”

Section: Introductionmentioning

confidence: 99%

Effects of hydroxytyrosol dose on the redox status of exercised rats: the role of hydroxytyrosol in exercise performance

Fazazi

Casuso

Aragón‐Vela

et al. 2018

Journal of the International Society of Sports Nutrition

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BackgroundHydroxytyrosol (HT) is a polyphenol found in olive oil that is known for its antioxidant effects. Here, we aimed to describe the effects of a low and high HT dose on the physical running capacity and redox state in both sedentary and exercised rats.MethodsMale Wistar rats were allocated into 6 groups: sedentary (SED; n = 10); SED consuming 20 mg/kg/d HT (SED20; n = 7); SED consuming 300 mg/kg/d HT (SED300; n = 7); exercised (EXE; n = 10); EXE consuming 20 mg/kg/d HT (EXE20; n = 10) and EXE consuming 300 mg/kg/d HT (EXE300; n = 10). All the interventions lasted 10 weeks; the maximal running velocity was assessed throughout the study, whereas daily physical work was monitored during each training session. At the end of the study, the rats were sacrificed by bleeding. Hemoglobin (HGB) and hematocrit (HCT) were measured in the terminal blood sample. Moreover, plasma hydroperoxide (HPx) concentrations were quantified as markers of lipid peroxidation.ResultsIn sedentary rats, HT induced an antioxidant effect in a dose-dependent manner without implications on running performance. However, if combined with exercise, the 300 mg/kg/d HT dosage exhibited a pro-oxidant effect in the EXE300 group compared with the EXE and EXE20 groups. The EXE20 rats showed a reduction in daily physical work and a lower maximal velocity than the EXE and EXE300 rats. The higher physical capacity exhibited by the EXE300 group was achieved despite the EXE300 rats expressing lower HGB levels and a lower HCT than the EXE20 rats.ConclusionsOur results suggest that a high HT dose induces a systemic pro-oxidant effect and may prevent the loss of performance that was observed with the low HT dose.

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“…Establishment and Drug Administration of the Mice Model of Colitis. Male ICR mice (6−8 weeks old, 28 ± 2 g) were obtained from Weitong Lihua Laboratory Animal Technology Co., Ltd. 1a), the free water method was allowed for the NC group mice during the experimental period (14 days), while the experimental group mice were perfused HT (10/50 mg/kg BW, the effective experimental dose of HT in mice is 5−100 mg/kg, and the polar toxicity experimental study showed that it had no toxicity to mice at the dose of 500 mg/kg 24,25 ) after being adapted to the environment for 7 days. Simultaneously, the same volume of normal saline (0.9% NaCl) was gavaged into NC and DSS group mice.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Hydroxytyrosol Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Inflammatory Responses, Intestinal Barrier, and Microbiome

Wang

Khan

et al. 2022

J. Agric. Food Chem.

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Hydroxytyrosol (HT), a polyphenol derived from olive oil, was examined against dextran sulfate sodium (DSS)-induced colitis to study its potential in preventing colitis and the underlying mechanisms involved. The low dose and high dose of HT used in mice were 10 and 50 mg/kg, respectively. Research findings have shown that HT is effective in preventing colitis by alleviating the signs of colitis. HT intervention significantly reduces colitis markers such as myeloperoxidase (MPO) and proinflammatory cytokine (IL-6, IL-1β, and TNF-α). Also, mice treated with a high dose of HT showed increased secretion of antioxidant enzymes (heme oxygenase-1 (HO) and anti-inflammatory cytokine (IL-10) by 2.32- and 2.28-fold, respectively, in comparison to the DSS-treated group. Modulation effects of HT on the antioxidant signal pathway (NRF2) and the inflammatory pathway (NF-κB) were confirmed. Meanwhile, HT promoted the regeneration of the intestinal barrier and maintained intestinal functional homeostasis by boosting the regeneration of goblet cells and the expression of mucin protein (Muc2) and tight junction (TJ) proteins (claudin-1, occludin, and Zonula Occludens-1). Moreover, HT intervention obviously transformed the gut microbiota, leading to a lower abundance of inflammation-related microbes (e.g., Bacteroidaceae and Desulfovibrionaceae) and a higher level of short-chain fatty acids (SCFAs) producing bacteria (e.g., Lachnospiraceae, Muribaculaceae, ASF356, and Colidextribacter). Scientific evidence for the beneficial effect of the “Mediterranean diet” (MD) on intestinal health was achieved by elucidating the alleviation mechanism of hydroxytyrosol on colitis.

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Toxicological evaluation of an olive extract, H35: Subchronic toxicity in the rat

Cited by 15 publications

References 32 publications

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract

Effects of hydroxytyrosol dose on the redox status of exercised rats: the role of hydroxytyrosol in exercise performance

Hydroxytyrosol Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Inflammatory Responses, Intestinal Barrier, and Microbiome

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