Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways

BackgroundEthnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats.Materials and methodsAnimals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group.ResultsBrugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats.ConclusionThe present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.

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“…The absorption was measured for 3 min at 480 nm. The unit of enzyme activity was written as U/min/mg ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism

Fatima

Anwar²,

Saleem³

et al. 2022

Front. Nutr.

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“…Selected mice were removed twice from the epididymis and smears of sperm specimens were made in a standard procedure that could be used for observation ( Wang et al, 2015 ). Sperm morphology was examined under a microscope, and normal and various types of abnormal sperms under the same field of view were counted and recorded ( Anwar et al, 2022 ).…”

Section: Experimental Design and Methodsmentioning

confidence: 99%

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents

Dong

Tang

et al. 2022

Front. Pharmacol.

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The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

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“…Sections were slashed at 5 mm and stained with hematoxylin and eosin. Histopathological modifications were studied under a photomicroscope ( Anwar et al, 2021a ).…”

Section: Methodsmentioning

confidence: 99%

Anti-arthritic and toxicological evaluation of ethanolic extract of Alternanthera bettzickiana in rats

Manan

Saleem²,

Ahmad³

et al. 2022

Front. Pharmacol.

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In many developing countries, medicinal plants have long been used for therapeutic purposes due to their low cost and toxicity. This study evaluated the safety and anti-arthritic potential of Alternanthera bettzickiana ethanolic extract (ABEE). Acute oral toxicity (OECD 425) was tested in the safety evaluation. A limit test was used to identify the LD50 value. For an acute oral toxicity study a dose of 2000 mg/kg of ABEE was given orally to the treatment group, and the control group received distilled water at a rate of 10 ml/kg. Biochemical, hematological, and histopathological analyses were performed after 14 days. A formaldehyde 2% w/v solution was injected via i.p. to rats of all groups to prepare the arthritic model. Five groups were divided into control (D.H2O), standard (Diclofenac), and three groups receiving the plant extract at dose levels of 125 mg/kg, 250 mg/kg, and 500 mg/kg respectively. Treatment was continued for 10 days. Paw diameter and hematological and biochemical variables were quantified. ELISA was performed for the estimation of inflammatory cytokines. In the acute oral toxicity study, no mortality or morbidity were observed, so the LD50 of this plant was greater than 2000 mg/kg. ABEE decreased the paw diameter with the restoration of hematological and biochemical changes. SOD and CAT levels were increased while decreasing the MDA, NO, TNF-α, and IL-6 levels in arthritic rats. It is concluded that the use of A. bettzickiana has low toxicity, and it can be used for the treatment of arthritis.

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Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways

Cited by 8 publications

References 45 publications

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents

Anti-arthritic and toxicological evaluation of ethanolic extract of Alternanthera bettzickiana in rats

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