Histological Changes in Renal, Hepatic and Cardiac Tissues of Wistar Rats after 6 Weeks Treatment with Bipyridine Gold (III) Complex with Dithiocarbamate Ligands

Bipyridine gold (III) dithiocarbamate compounds are Gold-III complexes with promising cytotoxic properties. In this study, the subacute toxicity of a Gold (III) complex with dithiocarbamate ligand was evaluated. In the acute toxicity component, an initial LD50 (38.46 mg/kg) was calculated by the administration of 50, 100, 200, 400, and 800 mg/kg of the compound to five groups of rats, respectively (n = 4 each). The sixth group was the control. The sub-acute toxicity component comprised the control group A (n = 6) and the study groups B (n = 10) and C (n = 4), which were administered 1 mL distilled water, 1/10 LD50 (3.8 mg/kg), and 1/5 LD50 (7.6 mg/kg), respectively, daily for 6 weeks. The alive animals were then sacrificed. Autopsy; preservation of renal, hepatic and cardiac tissue in buffered formalin; histopathological processing; microscopic evaluation; and comparison with the controls were sequentially conducted. In the subacute toxicity study at dosages of 3.8 mg/kg and 7.6 mg/kg, the renal tubules remained unaffected with no necrosis or vacuolization. Mild to moderate renal interstitial, hepatic capsular, lobular and portal inflammation along with mild focal hepatic vacuolization were present. At 3.8 mg/kg, the cardiac muscle fibers were unremarkable in 80% (n = 8) of the specimens, with mild focal hyalinization in 20% (n = 2) of the specimens. The same was observed in 50% (n = 2) of the specimens at 7.6 mg/kg. Variable congestion was evident in all of the groups. In the subacute toxicity study, the absence of renal tubular necrosis or vacuolization, the presence of mild inflammatory hepatic and renal alterations, and predominantly unremarkable cardiac muscle fibers suggest that Bipyridine gold (III)-dithiocarbamate is safe in animal studies and is a potential candidate for clinical trials.

Download Full-text

Withania frutescens. L Extract: Phytochemical Characterization and Acute and Repeated Dose 28-Day Oral Toxicity Studies in Mice

BioMed Research International ◽

10.1155/2020/1976298 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Abdelfattah EL Moussaoui ◽

Mohammed Bourhia ◽

Fatima Zahra Jawhari ◽

Imane Es-safi ◽

Syed Saeed Ali ◽

...

Keyword(s):

Acute Toxicity ◽

Oral Administration ◽

Biochemical Parameters ◽

Clinical Symptoms ◽

Toxicity Study ◽

Control Group ◽

Oral Toxicity ◽

Traditional Use ◽

Subacute Toxicity ◽

Acute Toxicity Study

Background. Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. Objective. The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. Materials and Methods. The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. Results. The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. Conclusion. The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.

Download Full-text

Acute and subacute toxicity of Ammi visnaga on rats

Interdisciplinary Toxicology ◽

10.2478/intox-2019-0004 ◽

2019 ◽

Vol 12 (1) ◽

pp. 26-35

Author(s):

Khaled M. M. Koriem ◽

Mahmoud S. Arbid ◽

Marwa A. El-Attar

Keyword(s):

Acute Toxicity ◽

Tap Water ◽

Oral Intake ◽

Ethanolic Extract ◽

Toxicity Study ◽

Control Group ◽

Subacute Toxicity ◽

Ammi Visnaga ◽

Group I ◽

Group 3

Abstract Ammi visnaga (Av) is a source of khellin where a tea made from the fruit of this plant was used as herbal medicine for kidney stones in Egypt. In the present research, the acute and subacute toxicity studies with oral intake of 150, 300 and 600 mg/kg of Av seed ethanolic extract in rats were done. In acute toxicity test, 4 groups of rats (n = 6/group: 3 males and 3 females) were chosen and the first control group received tap water, while the other three groups received Av seed ethanolic extract dissolved in tap water at doses of 150, 300, and 600 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, 72 rats (36 males and 36 females) were divided into 4 major groups; group I received tap water (control group), while animals in groups II, III, and IV (test groups) received oral intake of Av seed ethanolic extract dissolved in tap water at doses of 150, 300 and 600 mg/kg bwt, respectively. Each of this major group was subdivided consequently into 3 subgroups (n = 6/group: 3 males and 3 females) where brain tissue, blood sample, body and organs weights were recorded at the beginning and then after two and four weeks of the experiment for the determination of hematological, biochemical and histopathological changes in tissues (liver, kidney, brain, spleen, heart, testis and ovary). With regard to acute toxicity, Av seed ethanolic extract did not induce any toxic effects or death or any organ toxicity. In subacute toxicity study; oral intake with Av seed ethanolic extract did not reveal any change in body and organs weights, hematological parameters, serum glucose and cholesterol, brain neurotransmitters, liver and kidney functions, male and female hormones. In conclusion, Av seed ethanolic extract is nontoxic to liver, kidney, brain, spleen, heart, testis and ovary.

Download Full-text

Phytochemical Analysis and Toxicity Study of Aristolochia paucinervis Rhizomes Decoction Used in Moroccan Alternative Medicine: Histopathological and Biochemical Profiles

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1398404 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Mohammed Bourhia ◽

Ayoub Lahmadi ◽

Hafid Achtak ◽

Ayoub Touis ◽

Jamal Elbrahmi ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Alternative Medicine ◽

Toxicity Study ◽

Control Group ◽

Phytochemical Analysis ◽

Biochemical Alterations ◽

Subacute Toxicity ◽

Tubular Necrosis ◽

Test Population

Ethnopharmacological Relevance. Aristolochia paucinervis (A. paucinervis) (Aristolochiaceae) is a plant frequently used in Moroccan alternative medicine. The aim of the current study is to investigate the phytochemical composition of rhizomes decoction of A. paucinervis (RDA) and to evaluate its acute and subacute toxicity following the OECD guidelines. Materials and Methods. The qualitative phytochemical analysis of A. paucinervis was performed using standard qualitative phytochemical procedures. The acute toxicity of rhizomes decoction of the studied plant was evaluated in mice at single doses of 1, 2, and 4 g/kg of body weight for 14 days. In subacute toxicity study, the decoction was orally administered to mice at three different doses (0.5, 1, and 1.5 g/kg/day) for 28 days. Histopathological and biochemical parameters were investigated. Results. The preliminary phytochemical screening showed the presence of flavonoids, saponins, alkaloids, and polyphenols and the absence of anthraquinones, sterols, and terpenes. There was no mortality and no significant changes occurred in animals treated with 1 and 2 g/kg in the acute toxicity model. The signs of toxicity and morbidity were remarkable with the highest tested dose (4g/kg). LD50 (dose required to kill 50% of the test population) was determined as 4 g/kg. Repeated oral administration of 1 and 1.5 g/kg/day of RDA for 28 days induced significant disturbance of serum parameters (AST, ALT, LDH, urea, creatinine). Kidney and liver extracted from mice fed with 1 and 1.5 g/kg/day showed significant histopathological injuries as tubular necrosis, inflammatory infiltrate, tubular degeneration, necrosis, and hepatic cholestasis. Meanwhile, neither histopathological nor biochemical alterations were observed in mice treated with 0.5 g/kg/day of body weight in comparison to the control group. Conclusion. RDA showed toxicity in mice at a dose of 1 g/kg/day under subacute toxicity conditions. RDA is safe at a single dose inferior to 4 g/kg of body weight. The plant extract prepared by decoction showed more poisonous effect than the extract prepared by maceration at room temperature.

Download Full-text

Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Current Chemical Biology ◽

10.2174/2212796814999200818095036 ◽

2020 ◽

Vol 14 (3) ◽

pp. 187-195

Author(s):

Berhan Mengiste ◽

Tizazu Zenebe ◽

Kassahun Dires ◽

Ermias Lulekal ◽

Awol Mekonnen ◽

...

Keyword(s):

Acute Toxicity ◽

Essential Oil ◽

Eucalyptus Globulus ◽

Biochemical Parameters ◽

Skin Irritation ◽

Toxicity Study ◽

Subacute Toxicity ◽

Acute Toxicity Study ◽

Limit Test ◽

Ointment Formulation

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

Download Full-text