Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon‐induced reproductive toxicity in male rats

This study was designed to evaluate protective effect of Saussurea lappa root aqueous extract against Ethephon (2‐chloroethylphosphonic acid)‐induced reproductive toxicity in rats. Control group received distilled water. Second group was given S. lappa extract at a dose 50 mg/kg bw. Third group was given Ethephon at a dose 200 mg/kg bw. Fourth, fifth, and sixth groups were given S. lappa extract before, with or after Ethephon administration, respectively. Ethephon intoxication significantly decreased serum levels of follicle stimulating hormone, luteinizing hormone, testosterone, and prolactin. Also, it significantly decreased sperms count, vitality, morphology index, total motility, progressive motility, and proliferating cell nuclear antigen protein expressions in spermatogonia. However, it significantly increased sperms abnormalities, testicular tissue and DNA damages, P53 protein expressions, noprogressive motility, and immotile sperms. In contrast, S. lappa extract ameliorated these alterations. These results indicated that S. lappa had potential preventive and curative effects against Ethephon‐induced reproductive toxicity in rats.     

Anticancer activity of Saussurea lappa extract by apoptotic pathway in KB human oral cancer cells

Abstract

Context: Saussurea lappa Dence (Compositae) is used as a traditional herbal medicine to treat abdominal pain and tenesmus in East Asia. Current studies have shown that S. lappa has anticancer activity in divergent of cancer cells. However, the effects of S. lappa on oral cancer and its mechanisms of action have yet to be elucidated.

Objective: To explore its potential chemotherapeutic effects and mechanism of cell growth inhibition on human oral cancer cells.

Materials and methods: The dried roots of S. lappa were used in this study. Cell viability of KB cells was evaluated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay after treatment with 30?µg/ml of methanol extract from the dried roots of S. lappa. To understand whether its effect on cell death is related with apoptosis pathway, we performed DNA fragmentation assay, western blot, caspase activity assay and fluorescence-activated cell sorting (FACS) analysis.

Results: Treatment of S. lappa extract onto KB cells reduced cell viability significantly with an IC₅₀ value of 30?µg/ml. The formation of a DNA ladder was observed starting at the 24?h treatment. In western blotting analysis, the S. lappa extract induced the proteolytic processing of caspase-3, -9 and poly (ADP-ribose) polymerase, a significant increase of Bax and marked reduction of Bcl-2. We also confirmed the activation of caspase-3/-7 in living KB cells by fluorescence microscopy.

Conclusion: These results suggested that S. lappa extract inhibited cell proliferation through the apoptosis pathway in KB human oral cancer cells.     

Free radical scavenging potential of Saussarea costus

Saussurea costus (Falc.) Lipschitz from the family Asteraceae is an important medicinal drug, the roots of which are widely used in folk medicine. The antioxidant activity of the plant has been studied using its ability to scavenge DPPH, nitric oxide, superoxide radicals along with its ability to inhibit lipid peroxidation and GSH oxidation. The 1 mg mL(-1) extract had antioxidant activity with 85.2% reduction of DPPH and a 72.7% decrease in lipid peroxidation. It showed maximum inhibition of superoxide radical of 66.0%, and 58.4% inhibition of nitric oxide formation. The concentration of chlorogenic acid was 0.027% in the extract of S. costus. Thus, the therapeutic activity of the plant may be due to its antioxidant activity, probably as a result of the presence of chlorogenic acid.     

Burdock (Arctium lappa L.) root attenuates preneoplastic lesion development in a diet and thioacetamide‐induced model of steatohepatitis‐associated hepatocarcinogenesis

Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high‐income countries. Diet‐ and chemically induced rodent models have been applied for the translational study of NASH‐associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti‐inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH‐associated hepatocarcinogenesis. Eight‐week‐old male Wistar rats received choline‐deficient high‐fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione‐S‐transferase pi (GST‐P)⁺ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST‐P⁺ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki‐67) inside them. These findings suggest that short‐term exposure to BRE alleviated remodeling PNL development in NASH‐associated hepatocarcinogenesis.     

Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice

Saussurea lappa is a traditional herbal medicine used for to treat various inflammatory diseases. In this study, we investigated the protective effects of S. lappa against atopic dermatitis using human keratinocyte HaCaT cells, murine mast cell line MC/9 cells, and a house dust mite-induced atopic dermatitis model of Nc/Nga mice. Treatment with the S. lappa caused a significant reduction in the mRNA levels and production of inflammatory chemokines and cytokine, including thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) in tumor necrosis factor-α/interferone-γ-stimulated HaCaT cells. S. lappa exhibited the significant reduction in histamine production in MC/9 cells. In the atopic dermatitis model, S. lappa significantly reduced the dermatitis score and serum IgE and TARC levels. In addition, the back skin and ears of S. lappa-treated Nc/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. In conclusion, an extract of S. lappa effectively suppressed the development of atopic dermatitis, which was closely related to the reduction of chemokines and cytokine. Our study suggests that S. lappa may be a potential treatment for atopic dermatitis.     

A new sesquiterpene lactone with sulfonic acid group from Saussurea lappa

A new sesquiterpene lactone with an unusual sulfonic acid group, 13-sulfo-dihydrodehydrocostus lactone (1), was isolated from the roots of Saussurea lappa C. (Compositae), together with a known lignan (2). The structure of 1 was characterized on the basis of spectral evidence including 2DNMR studies. Compound 2 was obtained from this plant for the first time.     

Antilithiatic Effect of Melia azedarach. on Ethylene Glycol–Induced Nephrolithiasis in Rats

Abstract

The effect of the aqueous extract of Melia azedarach. Linn. (Meliaceae) against ethylene glycol–induced nephrolithiasis in male Wistar albino rats is summarized in this study. Lithiasis was induced in rats by administering 0.75% ethylene glycol in drinking water for 28 days and was manifested by high urinary calcium, phosphate, oxalate, and low urinary magnesium content. Simultaneous administration of aqueous extract of Melia azedarach. (AEMA; 250 mg/kg body weight) orally for 28 days along with ethylene glycol (0.75%) reduced urinary calcium, oxalate, phosphate, and elevated urinary magnesium level. It also increased the urine volume, thereby reducing the tendency for crystallization. The histopathological studies confirmed the induction of lithiasis as microcrystal deposition was observed in sections of kidney from animals treated with ethylene glycol. This was reduced, however, after treatment with the extract. These observations enable us to conclude that AEMA is effective against ethylene glycol–induced nephrolithiasis.     

Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol-induced lithiasis in male albino Wistar rats

The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment.     

Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents

We evaluated the toxicity of a semipurified extract (EPA fraction, containing caffeine and several flavan-3-ols and proanthocyanidins) of seeds of the native Amazon plant Paullinia cupana (guaraná) in rodents. Acute toxicity was tested in male Swiss mice, which received different doses orally (OR) and intraperitoneally (ip); control groups received water. These tests produced acute mortality, with LD₅₀ of 1.825 g/kg (OR) and 0.827 g/kg (ip), and a significant weight decrease in lungs of mice receiving a dose of 0.1 g/kg. In the repeated-dose toxicity test, the EPA was administered OR daily to male and female Wistar rats at doses of 30, 150, and 300 mg/kg/day/90 days. Their behavior, mortality, weight changes, laboratory tests, and the weights and histopathology of organs were evaluated. No rats died during the tests. Males dosed at 150 or 300 mg/kg gained weight more slowly and lost kidney weight (absolute and relative weights, compared to the control group). Hematological and biochemical tests showed few changes, differing somewhat between males and females; the histopathological evaluation indicated no significant changes. These results indicate that the EPA fraction of guaraná caused no toxicity in rats at the smallest dose evaluated (30 mg/kg). No other species was evaluated.     

Alcea rosea root extract as a preventive and curative agent in ethylene glycol-induced urolithiasis in rats

Introduction:

Alcea rosea L. is used in Asian folk medicine as a remedy for a wide range of ailments. The aim of the present study was to investigate the effect of hydroalcoholic extract of Alcea rosea roots on ethylene glycol-induced kidney calculi in rats.

Materials and Methods:

Male Wistar rats were randomly divided into control, ethylene glycol (EG), curative and preventive groups. Control group received tap drinking water for 28 days. Ethylene glycol (EG), curative and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation; preventive and curative subjects also received the hydroalcoholic extract of Alcea rosea roots in drinking water at dose of 170 mg/kg, since day 0 or day 14, respectively. Urinary oxalate concentration was measured by spectrophotometer on days 0, 14 and 28. On day 28, the kidneys were removed and examined histopathologically under light microscopy for counting the calcium oxalate deposits in 50 microscopic fields.

Results:

In both preventive and curative protocols, treatment of rats with hydroalcoholic extract of Alcea rosea roots significantly reduced the number of kidney calcium oxalate deposits compared to ethylene glycol group. Administration of Alcea rosea extract also reduced the elevated urinary oxalate due to ethylene glycol.

Conclusion:

Alcea rosea showed a beneficial effect in preventing and eliminating calcium oxalate deposition in the rat kidney. This effect is possibly due to diuretic and anti-inflammatory effects or presence of mucilaginous polysaccharides in the plant. It may also be related to lowering of urinary concentration of stone-forming constituents.KEY WORDS: Alcea rosea, malvaceae, kidney calculi, ethylene glycol, calcium oxalate     

Chelidonium majus leaves methanol extract and its chelidonine alkaloid ingredient reduce cadmium-induced nephrotoxicity in rats

The kidney is one of the critical target organs for chronic cadmium toxicity. Cadmium is a cumulative nephrotoxicant, and preferentially accumulates and persists in the kidneys. The natriuretic and antidiuretic effects of methyl alcohol extracts of Chelidonium majus L. (C. majus) leaves were evaluated in kidney of cadmium-intoxicated rats. Ninety-six male Sprague?CDawley Albino rats were divided into two major groups (toxicity and biochemical, 60 and 36 rats, respectively). There was a decrease in kidney weight and serum electrolytes, but an increase in urinary volume, excretion of electrolytes, serum urea and creatinine, after 9?weeks of cadmium chloride intoxication. Treatment of C. majus methyl alcohol extract for 10?weeks starting 1?week before cadmium administration shifted the above parameters towards the normal values. These results were supported by molecular and histological investigations. Treatment with C. majus methyl alcohol extract has natriuretic and antidiuretic effects against cadmium-induced nephrotoxicity in rats.     

Toxicity assessment of Ferula gummosa administration during pregnancy,lactation, and juvenile period in rat

Ferula gummosa is widely used in traditional medicine to treat a variety of ailments. This work evaluated the safety of F. gummosa root in pregnancy, lactation, and juvenile periods. This study was performed in three parts: (1) pregnant rats were received diet containing 0 (control), 150?, or 700?mg/kg of F. gummosa root during pregnancy; (2) Lactating rats were treated with diet containing the root (0, 150, or 700?mg/kg) during lactation period; (3) juvenile rats were received 4 weeks diet containing the root (0, 150, or 700?mg/kg). F. gummosa at both doses had no significant effects on the duration of pregnancy, maternal weight, and the number of delivered pups, but at dose of 700?mg/kg decreased birthweight of the pups. In lactation period, F. gummosa had no significant effects on mortality, body weight, body length, the weight of organs, and blood biochemical parameters of offspring. In juvenile rats, food consumption, body weight, and WBCs number were decreased in treated groups. No histopathological lesions were detected in the brain, heart, liver, lungs and kidney of offspring, and juvenile rats in treated groups. LC/MS/MS analysis confirmed systemic absorption of active constituents of the root by the oral route of administration. In conclusion, F. gummosa root did not produce significant toxic effects during pregnancy, lactation, and juvenile period. But, decrease in birthweight of delivered pups and in weight gain of juvenile rats should be considered in the long-term consumption of this plant.     

Co-administration of adjuvants along with Moringa oleifera attenuates beryllium-induced oxidative stress and histopathological alterations in rats

Abstract

Context: Moringa oleifera Lam. (Moringaceae) is a rich source of antioxidants. All parts of the plant are medicinally important and have been used as traditional medicine for a variety of human ailments in India.

Objective: Therapeutic efficacy of adjuvants with M. oleifera (MO) root extract was investigated against beryllium-induced oxidative stress.

Materials and methods: Hydroalcoholic (50% v/v) root extract of M. oleifera (150?mg/kg, p.o.) alone and combinations of M. oleifera with either piperine (2.5?mg/kg, p.o.) or curcumin (5.0?mg/kg, p.o.) daily for 1 week were administered in experimental rats against beryllium toxicity (1.0?mg/kg, i.p. daily for 5 weeks). Oxidative stress parameters including blood sugar, G-6-Pase in liver, and DNA damage were analyzed. Histopathological changes in liver and kidney were also observed.

Results: Beryllium enhanced lipid peroxidation (LPO), depleted reduced glutathione (GSH) and antioxidant enzymes activities, decreased blood sugar and G-6-Pase activity, and did not damage DNA. Histologically, liver was observed with structural loss and disintegration of hepatocytes, heavy vacuolation in hepatocytes, and kidney was observed with constriction of glomeruli and hypertrophy in epithelial cells of uriniferous tubules. Therapy of M. oleifera with piperine was effective; however, combination of M. oleifera with curcumin showed better therapeutic effect by reduction of LPO, elevated GSH level, maintained antioxidant enzymes activities, restored blood sugar, and G-6-Pase activity in liver together with almost normal histoarchitecture of liver and kidney.

Discussion and conclusion: Curcumin enhanced therapeutic efficacy of M. oleifera root extract and showed better antioxidant potential against beryllium toxicity.     

Protective effect of Aquilegia vulgaris (L.) against lead acetate-induced oxidative stress in rats

Oxidative stress has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activity of the ethanol extract of Aquilegia vulgaris (L.) against lead acetate (LA)-induced oxidative stress in male rats. Tested animals were treated orally with A. vulgaris extract (100 ppm) in combination with, before, or after LA treatment (20 ppm). The results indicated that the extract alone did not induce any significant changes in body weight gain, food intake, serum biochemical chemistry or the histological picture of the liver and kidney. However, it increased significantly the level of Glutathione (GSH). On the other hand, LA decreased food intake, body weight gain and induced oxidative stress as indicated by the significant changes in serum biochemical parameters and histological picture of liver and kidney and increased lipid peroxide and reduces GSH levels in liver tissues. The extract succeeded to improve the histological pictures of liver and kidney and the biochemical parameters towards the normal values of the control. Moreover, this improvement was pronounced in the animals treated with the extract after LA intoxication.     

Toxicological assessment of Ricinus communis Linn root extracts

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000?mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000?mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.     

Subacute toxicological evaluation of Asiasari radix methanol extract

Asiasari radix, a traditional herbal medicine commonly used to treat various diseases, currently has a lack of information about adverse effects. Safety information of A. radix and its extract is limited to its historical use. The safety of A. radix methanol extract was tested in an oral subacute 28-day toxicity study in both male and female Sprague-Dawley (SD) rats at doses of 50, 250, and 500?mg/kg/day. No mortality and significant signs of toxicity were observed in either the control or treated groups of both sexes. There were no significant differences in the body and organ weights or in food and water consumption. Hematological and biochemical parameters showed no changes in either the control or treated groups of both sexes. Pathologically, neither gross abnormalities nor histopathological changes were observed. Therefore, methanolic extract of A. radix appears to be safe and nontoxic in these studies, and a no observed adverse effect level in rats is established at 500?mg/kg/day, the highest dose tested.     

Subchronic toxicity of ethylene glycol in Wistar and F-344 rats related to metabolism and clearance of metabolites.

Ethylene glycol (CAS RN 107-21-1) can cause kidney toxicity via the formation of calcium oxalate crystals in a variety of species, including humans. Numerous repeated dose studies conducted in rats have indicated that male rats are more susceptible than female rats. Furthermore, subchronic and chronic studies using different dietary exposure regimens have indicated that male Wistar rats may be more sensitive to renal toxicity than male Fischer-344 (F-344) rats. This study was conducted to compare the toxicity of ethylene glycol in the two strains of rats under identical exposure conditions and to evaluate the potential contribution of toxicokinetic differences to strain sensitivity. Ethylene glycol was mixed in the diet at concentrations to deliver constant target dosage levels of 0, 50, 150, 500, or 1000 mg/kg/day for 16 weeks to groups of 10 male Wistar and 10 male F-344 rats based on weekly group mean body weights and feed consumption. Kidneys were examined histologically for calcium oxalate crystals and pathology. Samples of blood, urine, and kidneys from satellite animals exposed to 0, 150, 500, or 1000 mg/kg/day for 1 or 16 weeks were analyzed for ethylene glycol, glycolic acid, and oxalic acid. Treatment of Wistar rats at 1000 mg/kg/day resulted in the death of two rats; in addition, at 500 and 1000 mg/kg/day, group mean body weights were decreased compared to control throughout the 16 weeks. In F-344 rats exposed at 1000 mg/kg/day and in Wistar rats receiving 500 and 1000 mg/kg/day, there were lower urine specific gravities, higher urine volumes, and increased absolute and relative kidney weights. In both strains of rats treated at 500 and 1000 mg/kg/day, some or all treated animals had increased calcium oxalate crystals in the kidney tubules and crystal nephropathy. The effect was more severe in Wistar rats than in F-344 rats. Accumulation of oxalic acid in the kidneys of both strains of rats was consistent with the dose-dependent and strain-dependent toxicity. As the nephrotoxicity progressed over the 16 weeks, the clearance of ethylene glycol and its metabolites decreased, exacerbating the toxicity. Benchmark dose analysis indicated a BMDL05 for kidney toxicity in Wistar rats of 71.5 mg/kg/day; nearly fourfold lower than in F-344 rats (285 mg/kg/day). This study confirms that the Wistar rat is more sensitive to ethylene glycol-induced renal toxicity than the F-344 rat and indicates that metabolism or clearance plays a role in the strain differences.     

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrations exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m³. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.     

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats

Context: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. Objective: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. Materials and methods: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000?mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. Results: No evidence of maternal or foetal toxicity was observed. WSR extract caused no changes (p?Discussion and conclusion: Under the conditions of the study, the no-observed-effect level (NOEL) of WSR extract for maternal and developmental toxicity was concluded to be at least 2000?mg/kg/day.     

Ginseng aqueous extract ameliorates lambda‐cyhalothrin‐acetamiprid insecticide mixture for hepatorenal toxicity in rats: Role of oxidative stress‐mediated proinflammatory and proapoptotic protein expressions

This study was carried out to evaluate the protective effects of Panax ginseng aqueous extract (GAE) against hepatorenal toxicity induced by lambda‐cyhalothrin‐acetamiprid insecticide mixture in rats. A total of 32 male albino rats were assigned into four groups. Normal control group received distilled water. Insecticide control group intoxicated with the insecticide at a dose of 2.14 mg/kg b.wt orally day after day for 45 days. GAE control group was treated with GAE at a dose 200 mg/kg b.wt orally. GAE experimental group was administered GAE 1 hour before insecticide administration. Intoxication of rats with the insecticide caused a significant increase in serum aspartate aminotransferase and alanine aminotransferase activities and urea and creatinine levels as well as malondialdehyde concentration and proteins expression of caspase‐3 and induced nitric oxide synthase in hepatic and renal tissues. However, it decreased the serum levels of total protein and globulin and reduced the glutathione content and catalase activity in hepatic and renal tissues. In addition, insecticide induced histopathological alterations in both hepatic and renal tissues. In contrast, GAE modulated insecticide‐induced alterations in liver and kidney functions and structures as it ameliorated the effects of insecticide on the above mentioned parameters. These results indicated that GAE was a potent antioxidant agent that could protect rats against insecticide‐induced hepatorenal toxicity.