Ameliorative effect of certain antioxidants against mercury induced genotoxicity in peripheral blood lymphocytes

Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2?mM), curcumin (3.87?µM) and andrographolide (0.4?µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63?µM; 6.57?µM; 10.52?µM) of mercury salt (HgCl₂) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin?>?curcumin?>?andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective.     

Genotoxic effects of 4-methylimidazole on human peripheral lymphocytes in vitro

4-Methylimidazole (4-MEI), a heterocyclic organic chemical compound, is widely found in many foods and consumed by people worldwide. In this research, we aimed to investigate the cytotoxic and genotoxic effects of 4-MEI on human lymphocytes. For this purpose, human peripheral blood lymphocytes were treated with four concentrations of 4-MEI (300, 450, 600 and 750?μg/ml) for 24?h and 48?h periods and in vitro sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests were used. 4-MEI induced SCE in human peripheral lymphocytes at three highest concentrations (450, 600 and 750?μg/ml) in 48?h treatment period. CA and MN were induced in human peripheral lymphocytes at two highest concentrations of 4-MEI (600 and 750?μg/ml) in 24?h and 48?h treatment periods. The highest concentration of 4-MEI (750?μg/ml) induced MN formation more than the positive control MMC in 24?h treatment period. In addition, 4-MEI led to a decrease in MI at the highest concentration (750?μg/ml) in 24?h treatment period and at all concentrations in 48?h treatment period. 4-MEI reduced PI at all concentrations in 24?h treatment period and at all concentrations (expect the lowest) for 48?h treatment period. 4-MEI reduced nuclear division index (NDI) at 24 and 48?h treatment periods, even at the highest two concentrations, decreased more than the positive control MMC. Our results showed that 4-MEI pose a genotoxic and cytotoxic effects for human peripheral lymphocytes.     

Evaluation of ameliorative effect of curcumin on imidacloprid‐induced male reproductive toxicity in wistar rats

This study was undertaken to investigate the toxic effects of imidacloprid (IM) on male reproductive system and ameliorative effect of curcumin (CMN) in male Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100 mg/kg, body weight) were administered orally to the rats either alone or in combinations for a period of 28 days. At the end of experiment, male reproductive toxicity parameters (total sperm count and sperm abnormalities), testosterone level, steroidal enzymatic activity [3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐HSD], and oxidative stress indicators were estimated in testis and plasma. IM treatments resulted in significant decrease (p < 0.05) in total epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05) in sperm abnormalities. Activities of gamma‐glutamyl transpeptidase, lactate dehydrogenase‐x, and sorbitol dehydrogenase were significantly increased (p < 0.05), while, 3β‐HSD and 17β‐HSD enzymatic activity along with testosterone concentration in testis and plasma were decreased significantly (p < 0.05) in IM‐treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD, GPx, and GST. IM‐treated rats showed histopathological alterations in testis and epididymis. However, the reproductive toxicity parameters, oxidative stress indicators, and histopathological changes were minimized and functional restorations were noticed by co‐administration of CMN in IM‐treated rats. The results of this study suggest that IM‐induced male reproductive toxic effects could be ameliorated by CMN supplementation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1250–1263, 2016.     

In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes

Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10?µg/mL) for 24 and 48?h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48?h. PBs increased the CA at 24 and 48?h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48?h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48?h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48?h. However, proliferation index was not affected at all concentrations of PBs after 24?h treatment, although it was decreased at the highest concentration of PBs at 48?h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.     

The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes

Remeron (Mirtazapine) is an antidepressant drug which exerts its action by blocking presynaptic α-2-adrenergic receptors and postsynaptic serotonin types 2 and 3 receptors. In this in vitro analysis, human peripheral blood lymphocytes was treated by remeron (10, 25, 40 and 55 μg/mL) for 24 hours and 48 hours periods, then it was attempted to study of genotoxic and cytotoxic effects of the substance on human peripheral blood lymphocytes by some tests such as sister chromatid exchange (SCE), chromosomal abnormalities (CA) and micronucleus (MN) tests. Also proliferating effect of the substance was investigated. Remeron didn’t significantly cause chromosomal abnormalities and sister chromatid exchange while caused micronucleus at 40 μg/mL concentration and 24?h periodic time and increased proliferation index of the both 24 and 48 hours treated cells was decreased in a concentration manner. Also, exposing to the remeron for 24 and 48 hours leaded to a decrease in mitotic index and nucleus division index in the cells by concentration dependent manner. These findings showed that remeron did not have significantly genotoxic effects on human peripheral blood lymphocytes while it showed cytotoxic effects on the cells, which is the first report on genotoxic and cytotoxic properties of remeron.     

姜黄素对羟自由基及红细胞氧化性溶血的影响

目：探讨姜黄素（Ｃurcumin,Cur)清除羟自由基及防御脂质过氧化的能力。方法;利用Ｆenton反应生成羟自由基（OH）,由AAPH诱发红细胞氧化性溶血。结果：姜黄素对羟自由基有较强的清除作用（SC50为58．8μmol/L),其作用超过OH的特异性清除剂甘露醇（SC50为2．3μmol/L）;姜黄素（120μmol/L)能有效地抑制由AAPH诱发的红细胞氧化性溶血（抑制2h以上）,显示了较强的防御脂质过氧化的能力。结论：姜黄素对癌症及炎症等的治疗作用可能与其清除自由基及防御脂质过氧化的能力有关。     

Toxic effects induced by curcumin in human astrocytoma cell lines

Abstract

Objective: The objective of this study was to describe the toxicity induced by curcumin in human astrocytoma cell lines.

Methods: The effects induced by curcumin, at 100?µM for 24?h, were evaluated in four astrocytoma cell lines using crystal violet assay and through the evaluation of morphological and ultrastructural changes by electron microscopy. Also, the results of vital staining with acridine orange and propidium iodide for acidic vesicles and apoptotic bodies were analyzed and the expression of the Beclin1 gene was assessed by RT-PCR.

Results: The cells treated with curcumin at 100?µM induced an inhibitory concentration₅₀ of viability with morphological changes characterized by a progressive increase in large, non-acidic vesicles devoid of cytoplasmic components and organelles, but that conserved the cell nuclei. No DNA breakage was observed. The astrocytoma cells showed no apoptosis, necrosis or autophagy. Expression of BECLIN1 was not induced (p?<?0.05) by curcumin in the astrocytoma cells.

Conclusions: Curcumin at 100?µm induced a new type of death cell in astrocytoma cell lines.     

Ameliorative effect of propolis against cyclophosphamide-induced toxicity in mice

Abstract

Context: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent.

Objective: This study elucidates the protective effects of propolis against CTX-induced changes in mice.

Materials and methods: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200?µL of phosphate buffer saline (PBS), group 2 was injected with 100?mg/kg/d propolis, group 3 was injected with a single dose of CTX (200?mg/kg), and group 4 was injected with a single dose of CTX (200?mg/kg) followed by propolis (100?mg/kg) for 7 consecutive days. After 12?d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters.

Results: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved.

Conclusions: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.     

Nitroimidazole derivatives: non-randomness sister chromatid exchanges in human peripheral blood lymphocytes

Nitroimidazole derivatives exhibited genotoxic effect in different experimental conditions. This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of two 5-nitroimidazoles (ornidazole and metronidazole) using the in vitro human peripheral blood culture as experimental system. We observed that both derivatives showed a decrease in mitotic index (MI) (P < 0.001), an increase in sister chromatid exchanges (SCE) frequency (P < 0.001) and no modifications in cellular proliferation kinetics (CPK). As a null hypothesis we considered the assumption that larger chromosomes should harbor more SCE, which was viewed using a novel sequential G-band (400 band resolution)/SCE technique. The analysis showed highly significant chi square values (P < 0.001), indicating that SCE frequency per chromosome is not proportional to chromosome length. SCE could be considered an instability indicator due to the high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives. Copyright © 2008 John Wiley & Sons, Ltd.     

Protective effect of curcumin against formaldehyde‐induced genotoxicity in A549 Cell Lines

Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde‐induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde‐induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA–protein cross‐links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activity. In addition, the activation of NF‐κB and AP‐1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde‐induced oxidative stress, ameliorated DPCs and attenuated activation of NF‐κB and AP‐1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes

The multi-industrial applications of zinc oxide nanomaterials (ZnO NMs) lead to increasing exposure to humans. Though the ZnO nanoparticles (NPs) toxicity had been evaluated previously, toxicity of other forms of ZnO nanomaterials has not been evaluated. In this study, cytotoxicity and genotoxicity of four different types of ZnO NMs were evaluated using human peripheral blood lymphocytes (HPBL). In addition, the effect of anti-oxidants on ZnO NMs induced toxicity was also evaluated. Our results suggest that, size and shape of the nanomaterials have profound effects on their toxicity. The NPs and nanorods (NRs) possessed higher level of oxidative potential and ROS generation capacity than microparticles (MPs) and microrods (MRs). In contrast, MPs and MRs possessed higher level of lipid peroxidation capacity. The smaller NPs are more genotoxic while larger MPs and MRs were more cytotoxic in nature. Treatment with vitamin C or Quercetin significantly reduces the genotoxicity associated with ZnO NMs. The influence of size and shape in mediating NMs toxicity should be taken into account and the possible supplementation of anti-oxidants might mitigate the toxicity.     

In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes

Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0–50 μg/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of curcumin in the cell proliferation kinetics (CPK) by the proliferation index (PI) was also analyzed. The results indicated that high concentrations of curcumin induced CAs, mainly acentric fragments. SCEs rate was not statistically different from the control group in any curcumin treated cell group. The PI of cells treated with 2 and 5 μg/ml of curcumin were statistically significant from the control group and finally, the MI showed a tendency to increase in all the concentrations of curcumin tested. In conclusion, it can be assumed that the higher concentrations of curcumin evaluated have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.     

The protective effect of rutin against renal toxicity induced by lead acetate

Flavonoids are known to have powerful antioxidant activity that could play a protective role in oxidative stress-mediated diseases. Rutin (RT) is a flavonol glycoside composed of the flavonol quercetin and disaccharide rutinose. The protective effect of RT against nephrotoxicity induced by lead acetate was evaluated. Male albino rats of Wistar strain were used in this study. Animals were given lead acetate after a week of pretreatment with RT (50?mg/animal/day). Lead acetate exposure resulted in an increase in the uric acid, creatinine (CRN) and blood urea nitrogen (BUN) levels and a decrease in glutathione, superoxide dismutase, catalase and glutathione peroxidase (GPx) activities. Lead acetate treatment decreased GSH levels by 2-fold and the activities of GSH metabolizing enzymes decreased to a range of 2–2.5-fold in renal tissue (p?<?0.05). These changes were reversed significantly in animals receiving pretreatment of RT. Treatment of rats with RT prior to the treatment with lead resulted in the recovery of reduced levels of GSH, GSH-metabolizing enzymes to almost 85–90%. RT has a beneficial impact on lead-induced toxicity due to its scavenging and antioxidant effect in rats.     

Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes

Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug.

Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays.

Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00?μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48?h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H₂O₂ for isolated lymphocytes) were also maintained.

Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48?h, 25?μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25?μg/mL, 48?h). It significantly decreased the MI in all the concentrations at 24?h (except 0.78?μg/mL) and in the highest three concentrations at 48?h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index.

Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.     

姜黄素对大鼠心肌缺血性损伤的保护作用

目的观察姜黄素对大鼠心肌缺血的保护作用，探讨可能的作用机制。方法用大剂量异丙肾上腺素（Ｉｓｏ）造成大鼠心肌缺血性损伤模型，观察姜黄素３个剂量组和对照组大鼠的心电图、血清酶（ＣＰＫ，ＬＤＨ，ＧＯＴ）活性和血清中游离脂肪酸（ＦＦＡ）含量以及血清和心肌组织中超氧化物歧化酶（ＳＯＤ）的活性和脂质过氧化产物丙二醛（ＭＤＡ）的含量的变化。结果姜黄素可使Ｉｓｏ诱导的大鼠心电图缺血性改变（Ｊ点下移）减轻，抑制血清ＣＰＫ，ＬＤＨ，ＧＯＴ活性的升高，抑制ＦＦＡ含量的升高，并可降低缺血心肌组织中ＭＤＡ的含量，且这些作用呈现一定的剂量依赖关系。结论姜黄素可提高大鼠心肌耐缺氧能力，对大鼠心肌的缺血性损伤具有一定的保护作用。该保护作用的机制可能与其清除自由基功能有关。     

Sulforaphane mitigates cadmium-induced toxicity pattern in human peripheral blood lymphocytes and monocytes

Cadmium (Cd) is a highly toxic and widely distributed heavy metal that induces various diseases in humans through environmental exposure. Therefore, alleviation of Cd-induced toxicity in living organisms is necessary. In this study, we investigated the protective role of sulforaphane on Cd-induced toxicity in human peripheral blood lymphocytes and monocytes. Sulforaphane did not show any major reduction in the viability of lymphocytes and monocytes. However, Cd treatment at a concentration of 50 μM induced around 69% cell death. Treatment of IC₁₀-Cd and 100 μM sulforaphane combination for 24 and 48 h increased viability by 2 and 9% in cells subjected to Cd toxicity, respectively. In addition, IC₂₅ of Cd and 100 μM sulforaphane combination recovered 17–20% of cell viability. Cd induced apoptotic and necrotic cell death. Sulforaphane treatment reduced Cd-induced cell death in lymphocytes and monocytes. Our results clearly indicate that when the cells were treated with Cd + sulforaphane combination, sulforaphane decreased the Cd-induced cytotoxic effect in lymphocytes and monocytes. In addition, sulforaphane concentration plays a major role in the alleviation of Cd-induced toxicity.     

Deoxynivalenol induced oxidative stress and genotoxicity in human peripheral blood lymphocytes

Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study consists in using diverse cellular and molecular assays to evaluate cytotoxicity, genotoxicity as well as oxidative damage and to investigate their mechanisms in human peripheral blood lymphocytes. The human lymphocytes were cultured in eight different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6, 12 and 24 h. DON was able to decrease cell viability and cause damage to the membrane, the chromosomes or the DNA at all times of culture. It was also able to induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24 h. The results of the RT-PCR and the Western Blot indicated that DON is able to enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human lymphocytes. This mechanism is probably related to depletion of antioxidase and oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting the ability of DNA repair.     

镍,铅,汞化合物体外诱发人淋巴细胞（UDS）的检测

用人外周血淋巴细胞的非程序ＤＮＡ合成对镍、铅、汞化合物进行了测试，结果表明，这三种重金属都具有诱发ＵＤＳ的活性，并提示，受试重金属化合物达到一定浓度后，ＵＤＳ的ｃｐｍ值不再随剂量增高而增高，似乎在一定实验条件下ＵＤＳ的修复合成能力有一定限度。     

Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice

Cancer is the major cause of death and many factors that lead to its occurrences, such as environmental pollution and pesticides and other factors. Ehrlich carcinoma development depends on many things associated with the environment, nutrition, personal habits, and family history. The present study aimed to evaluate the potential protective effects of vitamin B17 (VB17) against Ehrlich ascites carcinoma (EAC) that induced kidney toxicity in female mice. The mice were divided into five groups (first group, control group; second group, VB17 group; third group, EAC group; fourth group, pretreated EAC with VB17; fifth group, cotreated EAC with VB17). Results showed the VB17 in pretreated (G4) and cotreated (G5) groups lead to an improvement in DNA damage and cytological examination, in addition significantly (P < .05) increase in Na⁺, red blood cell, hemoglobin, hematocrit value, mean corpuscular hemoglobin (MCH), and MCH concentration, whereas significantly (P < .05) decrease in urea, creatinine, K⁺, platelets, and white blood cells while insignificant (P < .05) changes in mean corpuscular volume when compared to the EAC group. Many histopathological changes were observed in kidney sections in EAC as marked damage and degenerated, glomerular atrophy, the Malpighian corpuscles that lost their characteristic configuration. On the other hand, a moderate improvement and arrangement in the kidney histological structure in pretreated VB17 + EAC, while a mild enhancement and arrangement of the kidney structure in cotreated EAC + VB17. In addition, depletion in renal P53 and PCNA protein expression compared with the EAC group. It could be concluded that VB17 has a potential renal protective effect against EAC cells induced kidney injury.     

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.