Comparative Study of the Possible Protective Effects of Cinnamic Acid and Cinnamaldehyde on Cisplatin‐Induced Nephrotoxicity in Rats

This study aimed to assess the protective effect of cinnamic acid (CA) and cinnamaldehyde (CD) against cisplatin‐induced nephrotoxicity. A single dose of cisplatin (5 mg/kg), injected intraperitoneally to male rats, caused significant increases in serum urea, creatinine levels, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum albumin, reduced glutathione, and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) of kidney as compared with the control group. On the other hand, administration of CA (50 mg/kg, p.o.) or CD (40 mg/kg, p.o.) for 7 days before cisplatin ameliorated the cisplatin‐induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress parameters. Furthermore, they reduced the histopathological changes induced by cisplatin. In conclusion, CA and CD showed protective effects against cisplatin‐induced nephrotoxicity where CD was more effective than CA; affects that might be attributed to their antioxidant activities.     

Thymol and Carvacrol Prevent Cisplatin‐Induced Nephrotoxicity by Abrogation of Oxidative Stress,Inflammation, and Apoptosis in Rats

The aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)‐induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase‐3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti‐inflammatory, and antiapoptotic activities.     

Hesperidin and Rutin,Antioxidant Citrus Flavonoids,Attenuate Cisplatin‐Induced Nephrotoxicity in Rats

This study aimed to assess the protective effect of hesperidin (HES) and rutin (RUT) against cisplatin‐induced nephrotoxicity in male rats. Cisplatin (5 mg/kg, intraperitoneal) caused significant increases in serum sodium, blood urea nitrogen, serum creatinine, total sodium and potassium excreted in urine, urine volume, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum total protein, creatinine clearance, reduced glutathione content of kidney, and kidney superoxide dismutase activity as compared with the control group. On the other hand, administration of HES (200 mg/kg, per oral [p.o.]) or RUT (30 mg/kg, p.o.) for 14 days with a single cisplatin dose on the tenth day ameliorated the cisplatin‐induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress biomarkers. Furthermore, the test drugs reduced the histopathological changes induced by cisplatin. In conclusion, HES and RUT showed protective effects against cisplatin‐induced nephrotoxicity.     

Protective effect of proanthocyanidins against doxorubicin‐induced nephrotoxicity in rats

Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi‐nephroprotective effect that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Effect of oral administration of Arabic gum on cisplatin-induced nephrotoxicity in rats

It has been recently postulated from our laboratory that Arabic gum (AG) offers a protective effect in the kidney of rats against nephrotoxicity induced by gentamicin via inhibiting lipid peroxidation. It has also recently shown a powerful antioxidant effect through scavenging superoxide anions. In this study we utilized a rat model of cisplatin (CP)-induced nephrotoxicity to determine its peak time following (1, 2, 5, and 7 days) of a single CP (7.5 mg/kg, i.p.) injection. Also, a possible protective effect of cotreatment with AG (7.5 g/kg/day p.o.) on CP-induced nephrotoxicity was investigated. Biochemical as well as histological assessments were carried out. CP-induced nephrotoxicity was manifested by significant elevations of the functional parameters blood urea, serum creatinine, and kidney/body weight ratio. Maximum toxic effects of CP were observed 5 days after its injection, while it started after day 1 in the biochemical parameters, such as glutathione depletion in the kidney tissue with concomitant increases in lipid peroxides and platinum content. Additionally, severe necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis were observed after 5 days in CP-treated animals. Five days after AG cotreatment with CP did not protect the kidney from the damaging effects of CP. However, it significantly reduced CP-induced lipid peroxidation. These findings suggest that lipid peroxidation is not the main cause of CP-induced nephrotoxicity but it is rather more dependent on other factors such as platinum disposition in renal interstitial tubules.     

Protective Effects of Pterostilbene against Acetaminophen‐Induced Hepatotoxicity in Rats

The present study was undertaken to evaluate the protective effect of pterostilbene against acetaminophen‐induced hepatotoxicity. Silymarin was used as a standard hepatoprotective agent. A single dose of acetaminophen (800 mg/kg i.p.), injected to male rats, caused significant increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, total cholesterol, triglycerides, tumor necrosis factor alpha, and hepatic contents of malondialdehyde, nitric oxide, caspase‐3, hydroxyproline, with significant decreases in serum HDL‐cholesterol, total proteins, albumin, and hepatic activities of reduced glutathione, superoxide dismutase and catalase as compared with the control group. On the other hand, administration of each of pterostilbene (50 mg/kg, p.o.) and silymarin (100 mg/kg, p.o.) for 15 days before acetaminophen ameliorated liver function and oxidative stress parameters. Histopathological evidence confirmed the protection offered by pterostilbene from the tissue damage caused by acetaminophen. In conclusion, pterostilbene possesses multimechanistic hepatoprotective activity that can be attributed to its antioxidant, anti‐inflammatory, and antiapoptotic actions.     

Modification of cyclophosphamide-induced clastogenesis and apoptosis in rats by alpha-lipoic acid

The aim of the present study was to investigate the protective efficacy of alpha-lipoic acid (LA) on the cyclophosphamide (CP)-induced chromosomal aberrations (CA) and apoptosis in the bone marrow of rats. Male Wistar rats of 140+/-20 g were categorized into eight groups. Five groups were administered CP (40 mg/kg body weight, intraperitoneally) to induce toxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to CP administration. A vehicle-treated control group and LA control groups were also included. Twenty-four hours after CP treatment, the frequency of CA in bone marrow cells were significantly increased in comparison with the controls. The CP-induced CA were associated with significant increase in DNA damage in the bone marrow as evidenced by increased single strand breaks, whereas in rats treated with LA and CP, the frequency of CA and single strand breaks were significantly decreased in comparison to those given CP alone. CP administration distinctly triggered the apoptotic and necrotic cell death, and LA pretreatment affected cell death by decreasing the number of apoptotic and necrotic cells. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage, indicating the dose dependent protective effect of LA. However, the protection by LA was not dependent on the time intervals between LA and CP administration. The results of this study illustrate the protective effect of LA on the CA and apoptosis induced by CP in the erythropoietic system of rats.     

Dehydroevodiamine.HCl prevents impairment of learning and memory and neuronal loss in rat models of cognitive disturbance

We previously reported that dehydroevodiamine.HCl (DHED) has anticholinesterase and antiamnesic activities. To verify the effects of DHED on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the rat using the passive avoidance and eight-arm radial maze tests. A single (20 mg/kg p.o.) and repeated (10 mg/kg p.o.) administrations of DHED could significantly reverse the latency time shortened by scopolamine (1 mg/kg i.p.) to control level. The impaired spatial working memory induced by scopolamine (1 mg/kg i.p.) was also improved significantly by a single injection (6.25 mg/kg i.p.) and repeated administrations of DHED (10 mg/kg p.o.) in the eight-arm radial maze test. In addition, we examined the effects of DHED on the memory impairment and the histological changes of the brain after unilateral electrolytic lesion of the entorhinal cortex (EC) and middle cerebral artery occlusion in rats. The cognitive deficits caused by EC lesion and middle cerebral artery occlusion were improved significantly by repeated administrations of DHED (6.25 mg/kg i.p.) after EC lesion or ischemic insult once a day for 7 days in the passive avoidance test. Histological analysis showed that the neuronal loss in the DHED-treated group was notably reduced in the hippocampal area (CA1) of ischemic rats and in the dentate gyrus and hippocampal area (CA1 and CA3) of EC-lesioned rats compared with the nontreated group. The infarction area was decreased significantly by a single administration of DHED (6.25 mg/kg i.p.) 30 min before ischemic insult for 6 h. These results suggest that DHED might be an effective drug for not only the Alzheimer's disease type, but also the vascular type of dementia.     

Thymol and Carvacrol Prevent Doxorubicin‐Induced Cardiotoxicity by Abrogation of Oxidative Stress,Inflammation, and Apoptosis in Rats

The aim of this study was to assess the possible protective effects of thymol and carvacrol (CAR) against doxorubicin (DOX)‐induced cardiotoxicity. A single dose of DOX (10 mg/kg i.v.) injected to male rats revealed significant increases in serum lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme‐MB, aspartate transaminase, tumor necrosis factor‐alpha, and cardiac troponin levels. It also increased heart contents of malondialdehyde and caspase‐3 accompanied by a significant reduction in heart content of reduced glutathione as well as catalase and superoxide dismutase activity as compared with the control group. In contrast, administration of thymol (20 mg/kg p.o.) and/or CAR (25 mg/kg p.o.) for 14 days before DOX administration and for 2 days after DOX injection ameliorated the heart function and oxidative stress parameters. Summarily, thymol was more cardioprotective than CAR. Moreover, a combination of thymol and CAR had a synergistic cardioprotective effect that might be attributed to antioxidant, anti‐inflammatory, and antiapoptotic activities.     

In vitro antioxidant activity of Juglans regia L. bark extract and its protective effect on cyclophosphamide-induced urotoxicity in mice

Walnut (Juglans regia L.) bark has been claimed to possess anti-inflammatory, blood purifying, anticancer, depurative, diuretic and laxative activities. It contains several therapeutically active constituents, especially polyphenols. We studied the antioxidant potential of aqueous extract of walnut bark and its modulatory effect on cyclophosphamide (CP)-induced urotoxicity in Swiss albino male mice. Free radical-scavenging activity of extract was assessed in four in vitro assays. The phenolic and flavonolic contents of the extract were also measured. Walnut bark extract treatment (150 mg/kg p.o. x 10 days) resulted in protective restoration of decreased antioxidants in CP-treated (18 mg/kg i.p. x 10 days) animals. CP treatment caused decreases in the activities of catalase (CAT), glutathione peroxidase (GP), glutathione reductase (GR) and glutathione S-transferase (GST) and in the glutathione (GSH) content in urinary bladder and a significant concomitant increase in lipid peroxidation (LPO). Administration of extract restored all the antioxidants significantly and lowered the elevated LPO in the bladder. A correlation between radical scavenging capacities of the extract with phenolic content was observed thus justifying its antioxidant potential against oxidative stress-mediated urotoxicity in mice. Walnut is reported to possess antiproliferative activity. Its protective effect on CP-induced toxicity in bladder is a promising activity, which warrants possible clinical investigations on this medicinal plant.     

Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents

This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53%), ethanol/HCl (75%), ibuprofen (52 %) and ischemia/reperfusion (43 %). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.     

Ethanol-Induced Oxidative Stress: The Role of Binaphthyl Diselenide as a Potent Antioxidant

It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. The protective effect of binaphthyl diselenide (NapSe)2 was investigated in ethanol (Etoh)-induced brain injury. Thirty male adult Wistar rats were divided randomly into five groups of six animals each and treated as follows: (1) The control group received the vehicle (soy bean oil, 1 mL/kg, p.o.). (2) Ethanol group of animals was administered with ethanol (70% v/v, 2 mL/kg, p.o.). (3) (NapSe)2 1 mg/kg, 1 mL/kg plus ethanol 70% (v/v, 2 mL/kg, p.o. (5) (NapSe)2 10 mg/kg, 1 mL/kg) plus ethanol 70% (v/v, 2 mL/kg, p.o). After acute treatment, all rats were sacrificed by decapitation. Evidence for oxidative stress in rat brain was obtained from the observed levels of thiobarbituric acid reactive species, of non-protein thiol (NPSH) groups, and of ascorbic acid, as well as from the activities of catalase (CAT) and of superoxide dismutase (SOD). (NapSe)2 compensated the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH, and ascorbic acid), and suppressed lipid peroxidation in rat brain resulting from Etoh administration. It was concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat brain. (NaPSe)2 at 5 mg/kg restored the antioxidant defenses in rat brain and mitigated the toxic effects of alcohol, suggesting that could be used as a potential therapeutic agent for alcohol-induced oxidative damage in rat brain.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

Hepatoprotective effects of saponarin, isolated from Gypsophila trichotoma Wend. on cocaine-induced oxidative stress in rats

The antioxidant effect of saponarin, which is the main flavone isolated from Gypsophila trichotoma Wend., and its protection against cocaine hepatotoxicity were investigated in male Wistar rats. The animals were treated with cocaine (40 mg/kg i.p.) alone and also after 3 consecutive days of pretreatment with saponarin (80 mg/kg p.o.). After 18 hours the rats were sacrificed by decapitation. The production of thiobarbituric acid reactive substances, reduced glutathione (GSH) and the activity of the following antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were assessed in liver homogenate. Administered alone, cocaine induced significant hepatotoxicity manifested with GSH depletion and reduced antioxidant defences. Saponarin pretreatment, however, decreased cocaine toxicity both by increasing GSH levels and antioxidant enzyme activities. The results of this study proved the antioxidant activity of saponarin and its protective effect against cocaine-induced oxidative stress and hepatotoxicity.     

Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury

Cyclophosphamide (CP) is a common anticancer drug, but its use in cancer treatment is limited due to its severe toxicities induced mainly by oxidative stress in normal cells. Reactive oxygen species (ROS) lead to multiple organ injuries, including the kidneys. Selenium (Se) is a nutritionally essential trace element with antioxidant properties. In the present study, the possible protective effect of Se on CP-induced acute nephrotoxicity was investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats in each. The control group received saline, and other groups were injected with CP (150 mg/kg), Se (0.5 or 1 mg/kg), or CP + Se intraperitoneally. Total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI), creatinine, and cystatin C (Cys C) levels were measured in the sera. In addition, kidney tissues were examined histologically. In the CP alone treated rats, creatinine, Cys C, TOS, and OSI levels increased, while TAC level decreased. CP-induced histological damages were decreased by co-treatment of Se and biochemical results supported the microscopic observations. In conclusion, our study points to the therapeutic potential of Se and indicates a significant role of ROS in CP-induced kidney toxicity.     

Bone Marrow and Adipose‐Derived Mesenchymal Stem Cells Alleviate Methotrexate‐Induced Pulmonary Fibrosis in Rat: Comparison with Dexamethasone

The present study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM‐MSCs) and adipose‐derived mesenchymal stem cells (AD‐MSCs) in methotrexate (MTX)‐induced pulmonary fibrosis in rats as compared with dexamethasone (Dex). MTX (14 mg/kg, as a single dose/week for 2 weeks, p.o.) induced lung fibrosis as marked by elevation of relative lung weight, malondialdehyde, nitrite/nitrate, interleukin‐4, transforming growth factor‐β1, deposited collagen, as well as increased expression of Bax along with the reduction of reduced glutathione content and superoxide dismutase activity. These deleterious effects were antagonized after treatment either with BM‐MSCs or AD‐MSCs (2 × 10⁶ cells/rat) 2 weeks after MTX to even a better extent than Dex (0.5 mg/kg/ for 7 days, p.o.). In conclusion, BM‐MSC and AD‐MSCs possessed antioxidant, antiapoptotic, as well as antifibrotic effects, which will probably introduce them as remarkable candidates for the treatment of pulmonary fibrosis.     

Synergistic effect of Nicorandil and Amlodipine on tissue defense system during experimental myocardial infarction in rats

The synergistic protective effect of Nicorandil (K_ATP channel opener) and Amlodipine (calcium channel blocker) on heart tissue antioxidant defense system and lipid profile were examined on isoproterenol induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg^–1 daily, i.p.) for 2 days showed significant changes in antioxidant defense system and lipid profile levels. Pretreatment with Nicorandil (2.5 mg kg^–1 daily, p.o.) and Amlodipine (5.0 mg kg^–1 daily, p.o.) for 3 days significantly prevented these alterations and restored the enzyme activities to near normal. These findings indicate the synergistic protective effect of Nicorandil and Amlodipine on tissue defense system and lipid metabolism during isoproterenol induced cardiac damage.     

Effect of bioactive tannoid principles of Emblica officinalis on iron-induced hepatic toxicity in rats.

The tannoid principles of the fruits of the plant Emblica officinalis Gaertn comprising of emblicanin A. emblicanin B, punigluconin and pedunculagin, have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin A (37%) and B (33%) enriched fraction of fresh juice of Emblica fruits (EOT), administered prophylactically (10, 20 and 50 mg/kg, p.o.) for 10 consecutive day, was found to inhibit acute iron overload (30 mg/kg, i.p.) hepatic lipid peroxidation and the increase of serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, used as markers of the induced hepatic dysfunction. A similar effect was produced by silymarin (20 mg/kg, p.o.), an antioxidant hepatoprotective agent. The results support the use of Emblica fruits for hepatoprotection in Ayurveda.     

Protective Effect of Seleno-<Emphasis Type="SmallCaps">l</Emphasis>-Methionine on Cyclophosphamide-Induced Urinary Bladder Toxicity in Rats

Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. Its urotoxicity may cause dose-limiting side effects like hemorrhagic cystitis. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the urothelial injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the urotoxicity of CP and the possible protective effects of seleno-l-methionine (SLM) on urinary bladder of rats were investigated. Intraperitoneal (i.p.) administration of 50, 100, or 150 mg/kg CP induced cystitis, in a dose-dependent manner, as manifested by marked congestion, edema and extravasation in rat urinary bladder, a marked desquamative damage to the urothelium, severe inflammation in the lamina propria, focal erosions, and polymorphonuclear (PMN) leukocytes associated with occasional lymphocyte infiltration determined by macroscopic and histopathological examination. In rat urinary bladder tissue, a significant decrease in the endogenous antioxidant compound glutathione, and elevation of lipid peroxidation were also noted. Pretreatment with SLM (0.5 or 1 mg/kg) produced a significant decrease in the bladder edema and caused a marked decrease in vascular congestion and hemorrhage and a profound improvement in the histological structure. Moreover, SLM pretreatment decreased lipid peroxide significantly in urinary bladder tissue, and glutathione content was greatly restored. These results suggest that SLM offers protective effects against CP-induced urinary bladder toxicity and could be used as a protective agent against the drug toxicity.     

Ameliorative Effect of Carvacrol on Cisplatin‐Induced Reproductive Damage in Male Rats

Cisplatin (CP) treatment causes the damage in male reproductive system. Carvacrol (CARV) is an antioxidant that is naturally found in some plants. We aimed to investigate the effect of CARV on CP‐induced reproductive toxicity in male rats. Eighteen adult male Sprague–Dawley rats were used. The control group (n = 6) was treated orally with physiological saline (PS) daily for 14 days and a single intraperitoneal (IP) PS injection on day 10. The CP group (n = 6) was administered with daily oral PS for 14 days and a single IP injection of 10 mg/kg CP on day 10. The CARV + CP group (n = 6) was treated with daily 75 mg/kg oral CARV for 14 days and a single IP injection of 10 mg/kg CP on day 10. CP treatment caused the damage on some spermatological parameters (motility, live sperm rate, and abnormal sperm rate), increased the oxidative stress, and induced testicular degeneration and apoptosis. However, CARV treatment mitigates CP‐induced reproductive toxicity.