Beneficial effects of Salvia officinalis essential oil on vanadium-induced testicular injury, DNA damage and histological alterations in Wistar rats.

Vanadium has been shown to catalyze the generation of reactive oxygen species. Since free radical production and lipid peroxidation are potentially important mediators in testicular physiology and pathophysiology, the present study was conducted to elucidate vanadium-induced oxidative damage in rat testis and the ameliorative role of Salvia officinalis essential oil (SEO) against the adverse effects of this heavy metal. Adult male Wistar rats were treated daily during 10 days either with ammonium metavanadate (5 mg/kg bw, intraperitoneally), SEO (15 mg/kg bw, orally) or their combination. A group of rats receiving daily a saline solution served as a negative control. Vanadium treatment induced a significant decrease in body and reproductive organ weights, serum testosterone level and sperm number and motility. An increase in lipid peroxidation and protein oxidation as well as a marked inhibition in the activities of antioxidant enzymes in the testes and seminal vesicles indicated the occurrence of oxidative stress after vanadium toxicity. Histopathological changes in testis and seminal vesicles were also observed following vanadium administration. However, co-administration of SEO to vanadium-treated rats resulted in an appreciable improvement of these parameters, emphasizing the therapeutic effects of SEO. It can be suggested that SEO mitigates vanadium-induced reproductive damage due to its antioxidant capacity. Thus, we can hypothesize that SEO supplementation could protect against vanadium poisoning.

Antioxidant role of selenium against maneb-induced cardiotoxicity in mice.

The current study was conducted to assess the beneficial effect of selenium (Se) on maneb-induced cardiotoxicity and fatty acid alterations in adult mice. Swiss albino male mice were assigned into four experimental groups. The first group consisted of negative controls. The second group represented the positive controls where mice received daily, via the diet, sodium selenite at a dose of 0.2 mg/kg. For the third group, mice were subjected to intraperitoneal injections of maneb (30 mg/kg BW). The fourth group (MB+Se) received daily the same dose of maneb as group 3 along with sodium selenite at the same dose as group 2. Mice exposure to maneb caused cardiotoxicity as indicated by an increase in malondialdehyde, hydrogen peroxide, and protein carbonyl levels, and an alteration of the antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and vitamin C). Plasma lactate dehydrogenase activity and total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased, while high-density lipoprotein cholesterol level decreased. Results showed also a decrease in the amount of n-3 PUFA, docosahexaenoic, docosapentaenoic, and eicosapentaenoic acids. However, an increase in the levels of MUFA, cis-vaccenic, and palmitoleic acids was observed. Co-administration of Se restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Selenium could be a useful and efficient agent against maneb-induced cardiotoxicity.

Salvia officinalis mitigates uterus and liver damages induced by an estrogen deficiency in ovariectomized rats.

The present study evaluated the antioxidant activity of Salvia officinalis (sage) and its protective effect on estrogen deficiency in ovariectomized rats. Female Wistar rats were treated during either 15 or 30 days as follows: group C: negative controls, group S: positive controls treated with sage leaves, ovariectomized rats (group OVX) and ovariectomized rats receiving either sage (OVX-S) or hormonal (Group OVX-E) treatments, respectively. After 15 and 30 days of treatments, OVX rats showed a gain in body weight and an increase of absolute and relative liver weights. Meanwhile, absolute and relative uterus weights were decreased. Moreover, ovariectomy altered plasma transaminases' activities, lipid profile, and disrupted the redox status of liver and uterine tissues. It affected also the reproductive tract by decreasing the uterus glycogen content and plasma LDH activity. Supplementation of sage via the diet reduced weight gain and oxidative stress resulting from estrogen deficiency. PRACTICAL APPLICATIONS: During menopause, sexual hormone deficiency, especially estrogen, causes several morphological and physiological disturbances in liver and uterus tissues. In fact, the body weight gain and disturbances of redox status in liver and uterus were the main health problems detected after menopause. Sage leaves, used as medicinal plant, exerted its beneficial effects in the management of menopause disorders. As an important source of antioxidants, sage leaves could prevent obesity and oxidative damage in the liver and uterus resulting from estrogen deficiency.

Anti-oxidant and hepatoprotective effects of Salvia officinalis essential oil against vanadium-induced oxidative stress and histological changes in the rat liver.

The present study was designed to evaluate the protective effects of Salvia officinalis essential oil (SOEO) against vanadium-induced hepatotoxicity in Wistar rats. Animals were divided into three groups: the first group served as the control (C), where rats received daily 0.5 mL of saline solution (0.9%) given by intraperitoneal (i.p.) way. Rats in the second group (V) received daily by i.p. way 5 mg/kg BW of NH4VO3 (V). Rats in the third group (SV) received daily V (5 mg/kg BW) by i.p. way and SOEO (15 mg/kg BW) by gavage. Animals were sacrificed after 4 or 10 days of treatment. Administration of V increased plasma ALT, AST, ALP, and LDH activities, and cholesterol, bilirubin, triglyceride, and NO levels in rats and reduced anti-oxidant enzyme activities in the liver. Treatment with SOEO significantly attenuated these changes. Moreover, the histopathological changes and the overexpression of Hsp72/73 proteins induced by V were significantly improved by SOEO. Therefore, our results suggested that SOEO could protect against V-induced oxidative damage in rat livers. The hepatoprotective effect of SOEO might be attributed to its modulation of detoxification enzymes and/or to its anti-oxidant and free radical scavenging effects.

The potential toxic effects of hexavalent chromium on oxidative stress biomarkers and fatty acids profile in soft tissues of Venus verrucosa.

Hexavalent chromium (chromium (VI)), a highly toxic heavy metal, is a common pollutant of aquatic ecosystems. The present study aimed to elucidate the potential toxic effects of chromium (VI) on oxidative stress biomarkers and fatty acids profile in the gills and digestive gland of Venus verrucosa, an ecologically and economically important bivalve species. Three doses of chromium (VI) (1, 10 and 100 µg.L-1) were chosen for V. verrucosa exposure during 7 days under controlled conditions. A significant increase in the levels of malondialdehyde, lipid hydroperoxides and hydrogen peroxide was observed in the gills and digestive gland of chromium (VI)-exposed V. verrucosa as compared to the control group. Furthermore, an induction of enzymatic antioxidant activities (superoxide dismutase, glutathione peroxidase and glutathione S-transferase) and an enhancement of non-enzymatic antioxidant levels (non-protein thiols, glutathione and vitamin C) were marked. An alteration of fatty acids composition was also noted following chromium (VI) exposure. The obtained results highlighted the importance of assessing oxidative damage biomarkers and fatty acids profile in the study of chromium (VI)-induced toxicity in V. verrucosa.

The protective effects of Salvia officinalis essential oil compared to simvastatin against hyperlipidemia, liver, and kidney injuries in mice submitted to a high-fat diet.

The present study was undertaken to evaluate the effects of Salvia officinalis essential oil (SEO) and simvastatin in hyperlipidemic mice. Animals were randomly divided into four groups. The control group received a standard diet. The high-fat diet (HFD) group received HFD. The third and fourth groups received HFD associated either with simvastatin (2.5 mg/kg bw) or with SEO (4 mg/kg bw). All animals were sacrificed after 8 weeks of treatment. SEO and simvastatin reduced in HFD mice body weight gain, hyperlipidemia, disruption of liver and renal functions and reactive oxygen species production. In fact, total cholesterol, triglycerides, total lipids, and low-density lipoprotein cholesterol levels, as well as aspartate transaminase, alanine transaminase, gamma-glutamyltranspeptidase and lactate dehydrogenase activities were reduced, while fecal lipids increased compared to those of HFD mice. The lipid-lowering effect of SEO was more effective than that of simvastatin. PRACTICAL APPLICATIONS: High-fat diet provokes hyperlipidemia, atherosclerosis, and abnormal lipid metabolism leading to the development of hepatic and renal dysfunctions as well as perturbations of the antioxidant status in liver and kidney. The results of this research highlight the beneficial effects of SEO in the management of these disorders without inducing side effects; in fact, the plant essential oil decreased lipids and improved the antioxidant status more than did a synthetic drug.

Zinc alleviates maneb-induced kidney injury in adult mice through modulation of oxidative stress, genotoxicity, and histopathological changes.

Zinc is one of the important essential trace minerals to human health due to its antioxidant properties. The present study was conducted to elucidate its potential protective role against maneb-induced nephrotoxicity. For this purpose, animals were randomly divided into four groups of six each. Mice of group I (negative controls) have received daily 0.5 ml of distilled water, a solvent of maneb. Mice of group II (MB) have received 30 mg/kg bw of maneb daily by intraperitoneal way. Mice of group III (MB + Zn) have received the same dose of maneb as group II, along with ZnSO4 (30 mg/kg bw) daily. Mice of group IV (Zn), considered as positive controls, have received the same dose of ZnSO4 as group III daily. Our results revealed that ZnSO4 co-administration to maneb-treated mice decreased kidney levels of malondialdehyde, hydrogen peroxide, protein carbonyls, and advanced oxidation protein products; the levels of non-enzymatic antioxidants like vitamin C, glutathione, and metallothionein. It recovered the alteration of antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and attenuated DNA fragmentation. Furthermore, this essential trace element was also able to alleviate kidney biomarkers' alterations by lowering plasma levels of creatinine, urea, uric acid, and lactate dehydrogenase. In addition, the histopathological changes induced by maneb were improved following zinc administration. Our results indicated that zinc might be beneficial against maneb-induced renal oxidative damage in mice.

Glyphosate disrupts redox status and up-regulates metallothionein I and II genes expression in the liver of adult rats. Alleviation by quercetin.

The present work evaluated the possible protective effects of quercetin against glyphosate-induced hepatotoxicity in adult rats. Rats were randomly divided into three groups: a control group (C), a glyphosate-treated group (Gly) and a group treated with both glyphosate and quercetin (Gly+QE). During the experimental period (15 days), glyphosate (50 mg/kg b.w.) was administered every two days by intraperitoneal way while quercetin (20 mg/kg b.w./day) was administered daily by gavage. Glyphosate-induced hepatic oxidative stress was evidenced by the increased levels of malondialdehyde, hydrogen peroxide, advanced oxidation protein products and protein carbonyls with a significant decrease in enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (non-protein thiols, glutathione, vitamin C) antioxidants. Plasma biomarkers of hepatotoxicity (AST, ALT, ALP, γ-GT, albumin) were also altered. Moreover, glyphosate induced DNA damage, up-regulated metallothionein (MT I and MT II) genes expression and provoked histopathological changes in rats' liver. Quercetin supplementation to glyphosate-treated rats markedly ameliorated all the parameters indicated above as well as the liver histoarchitecture. Therefore, quercetin might have beneficial effects against glyphosate-induced hepatotoxicity in rats.

Penconazole alters redox status, cholinergic function and lung's histoarchitecture of adult rats: Reversal effect of vitamin E.

The present study pertains to the possible adverse effects of penconazole exposure on the lung of adult rats, and to the potential ability of vitamin E (Vit E) in mitigating the toxicity induced by this fungicide. Male Wistar rats were divided into four groups of six animals each: Group I (Controls): rats drank distilled water; Group II (PEN): rats received, by gavage, 50 mg/kg body weight (1/40 LD50) of penconazole every 2 days during 10 days; Group III (Vit E): rats received daily 100 mg α-tocopherol acetate/kg body weight during 10 days by gavage; and Group IV (Vit E + PEN): rats received both vitamin E (100 mg α-tocopherol acetate/kg body weight) and penconazole (50 mg/kg body weight), being vitamin E given as a daily dosage and penconazole every 2 days, by gavage during 10 days. Results showed that penconazole induced oxidative stress in the lung demonstrated by an increase in malondialdehyde (+77%), hydrogen peroxide (+58%) and advanced oxidation protein product (+22%) levels, as compared to the controls. Furthermore, a decrease in the activities of catalase (-41%), superoxide dismutase (-45%), glutathione peroxidase (-23%) and acetylcholinesterase (-67%), and an increase in the levels of non-protein thiols (+17%), glutathione (+7%) and vitamin C (+44%) were registered. Abnormalities in lung histological sections such as alveolar edema, infiltration of inflammatory cells (leukocytes) and emphysema, were also observed following penconazole exposure. Vitamin E ameliorated the biochemical parameters, as well as the histological impairments induced by this fungicide. In conclusion, our study demonstrated that vitamin E, a natural antioxidant, was effective in alleviating penconazole-induced lung damage in Wistar rats.

Effects of co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats.

Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA3) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA3 (200 mg/L) via drinking water. IMI associated or no with GA3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA3-induced nephrotoxicity. Co-exposure to IMI and GA3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

Zinc and selenium modulate barium-induced oxidative stress, cellular injury and membrane-bound ATPase in the cerebellum of adult rats and their offspring during late pregnancy and early postnatal periods.

CONTEXT: Barium (Ba) may induce oxidative stress leading to tissues injury. OBJECTIVE: Our study investigated the therapeutic efficiency of zinc (Zn) and selenium (Se) against neurotoxicity induced by Ba in adult rats and their progeny. MATERIAL AND METHODS: Pregnant rats are exposed either to Ba (67 ppm), Ba + Zn, Ba + S or to only Zn and Se. RESULTS: In Ba-treated rats, there was an increase of MDA, H2O2, AOPP levels and SOD activity in the cerebellum of dams and their pups, a decrease in GPx, CAT, AChE, Na+K+-ATPase and Mg2+-ATPase activities, GSH and NPSH levels. These changes were confirmed by histological damages. Co-administration of Zn or Se to Ba-treated rats ameliorated the biochemical and histological aspects. CONCLUSION: Our results revealed that Zn and Se have shown promising effects against Ba toxicity in the cerebellum of adult rats and their suckling pups.

Effects of barium graded doses on redox status, membrane bound ATPases and histomorphological aspect of the liver in adult rats.

Nowadays, liver diseases constitute a major health problem in the world. The objective of the present study was to elucidate the hepatotoxicity induced by barium chloride (BaCl2) administered at graded doses in order to evaluate redox state and membrane-bound ATPases in the liver of adult rats. Our results showed, after 21 days of treatment with barium at doses 67 150 and 300 ppm, an increase in hepatic biomarkers such as AST, ALT and GGT activities and in bilirubin and albumin levels. A significant increase in MDA, LOOHs, H2O2, AOPP and PCO levels in liver of treated rats with graded doses of BaCl2 was also observed suggesting the implication of oxidative stress with a significant relation between dose and response. Moreover, LDH activity increased in plasma and decreased in liver of all treated groups. Antioxidant activities of glutathione peroxidase and catalase decreased, especially with the highest dose of barium, indicating a failure of antioxidant system defense. Additionally, the activities of Na+K+-ATPase and Mg2+-ATPase significantly decreased in all treated groups. Our biochemical findings were supported by histological observations. These results highlight the subchronic hepatotoxicity of barium.

Nitraria retusa fruit prevents penconazole-induced kidney injury in adult rats through modulation of oxidative stress and histopathological changes.

CONTEXT: Nitraria retusa (Forssk.) Asch. (Nitrariaceae) is a medicinal plant which produces edible fruits whose antioxidant activity has been demonstrated. OBJECTIVE: The current study elucidates the potential protective effect of N. retusa fruit aqueous extract against nephrotoxicity induced by penconazole, a triazole fungicide, in the kidney of adult rats. MATERIALS AND METHODS: Adult Wistar rats were exposed either to penconazole (67 mg/kg body weight), or to N. retusa extract (300 mg/kg body weight) or to their combination. Penconazole was administered by intra-peritoneal injection every 2 days from day 7 until day 15, the sacrifice day, while N. retusa extract was administered daily by gavage during 15 days. Oxidative stress parameters, kidney biomarkers and histopathological examination were determined. RESULTS: Nitraria retusa extract administration to penconazole treated rats decreased kidney levels of malondialdehyde (-10%), hydrogen peroxide (-12%), protein carbonyls (PCOs, -11%) and advanced oxidation protein products (AOPP, -16%); antioxidant enzyme activities: catalase (-13%), superoxide dismutase (-8%) and glutathione peroxidase (GPx, -14%), and the levels of non-enzymatic antioxidants: non-protein thiols (-9%), glutathione (-7%) and metallothionein (-12%). Furthermore, this plant extract prevented kidney biomarker changes by reducing plasma levels of creatinine, urea, uric acid and LDH and increasing those of ALP and GGT. Histopathological alterations induced by penconazole (glomeruli fragmentation, Bowman's space enlargement, tubular epithelial cells necrosis and infiltration of inflammatory leucocytes) were attenuated following N. retusa administration. DISCUSSION AND CONCLUSION: Our results indicated that N. retusa fruit extract had protective effects against penconazole-induced kidney injury, which could be attributed to its phenolic compounds.

Protective effects of dietary selenium and vitamin C in barium-induced cardiotoxicity.

Several metals including barium (Ba) known as environmental pollutants provoke deleterious effects on human health. The present work pertains to the potential ability of selenium (Se) and/or vitamin C, used as nutritional supplements, to alleviate the toxic effects induced by barium chloride (BaCl2) in the heart of adult rats. Animals were randomly divided into seven groups of six each: group 1, serving as negative controls, received distilled water; group 2 received in their drinking water BaCl2 (67 ppm); group 3 received both Ba and Se (sodium selenite 0.5 mg kg-1 of diet); group 4 received both Ba and vitamin C (200 mg kg-1 bodyweight) via force feeding; group 5 received Ba, Se, and vitamin C; and groups 6 and 7, serving as positive controls, received either Se or vitamin C for 21 days. The exposure of rats to BaCl2 caused cardiotoxicity as monitored by an increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, a decrease in Na+-K+ adenosine triphosphatase (ATPase), Mg2+ ATPase, and acetylcholinesterase activities and in antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and nonprotein thiols). Plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels increased, while high-density lipoprotein-cholesterol level decreased. Coadministration of Se and/or vitamin C restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Se and vitamin C may be a promising therapeutic strategy for Ba-induced heart injury.

Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach.

Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl3) (400 ppm) via drinking water, AlCl3 associated with Na2SeO3 (0.5 mg/kg of diet), or only Na2SeO3. Exposure of rats to AlCl3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non-enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin-laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage.

Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide.

Aluminum chloride (AlCl3) and acrylamide (ACR) are well known as environmental pollutants inducing oxidative stress. Our study investigated the effects of these contaminants and if the hydrophilic fraction of extra virgin olive oil was able to prevent lung oxidative stress and DNA damage. Animals were divided into four groups of six each: group 1, serving as controls, received distilled water; group 2 received in drinking water aluminum chloride (50 mg/ kg body weight) and by gavage acrylamide (20 mg/kg body weight); group 3 received both aluminum and acrylamide in the same way and the same dose as group 2 and hydrophilic fraction from olive oil (OOHF) (1 ml) by gavage; group 4 received only OOHF by gavage. Exposure of rats to both aluminum and acrylamide provoked oxidative stress in lung tissue based on biochemical parameters and histopathological alterations. In fact, we have observed an increase in malondialdehyde (MDA), H2O2, and advanced oxidation protein product (AOPP) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH), and vitamin C levels. Activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were also decreased. Histopathological changes in lung tissue were noted like emphysema, vascular congestion, and infiltration of inflammatory cells. A random DNA degradation was observed on agarose gel in the lung of AlCl3 and acrylamide (ACR)-treated rats. Co-administration of OOHF to treated rats improved biochemical parameters to near control values and lung histoarchitecture. The smear formation of genomic DNA was reduced. The hydrophilic fraction of extra virgin olive oil might provide a basis for developing a new dietary supplementation strategy in order to prevent lung tissue damage.

Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats.

Hepatotoxicity, induced by aluminium chloride (AlCl3), has been well studied but there are no reports about liver metallothionein (MT) genes induction. Therefore, it is of interest to establish the mechanism involving the relation between MT gene expression levels and the oxidative stress status in hepatic cells of aluminium-treated rats. Aluminium (Al) was administered to rats in their drinking water at a dose of 50 mg/kg body weight for three weeks. AlCl3 provoked hepatotoxicity objectified by an increase in malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein products (AOPP), protein carbonyls (PCO) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH) and vitamin C. CAT and Glutathione peroxidase (GPx) activities were decreased while Mn-SOD gene expression, total Metallothionein content and MT I and MT II genes induction were increased. There are changes in plasma of some trace elements, albumin levels, transaminases, LDH and ALP activities. All these changes were supported by histopathological observations.

Improvement of Heart Redox States Contributes to the Beneficial Effects of Selenium Against Penconazole-Induced Cardiotoxicity in Adult Rats.

The present study was performed to evaluate the protective effect of selenium (Se) against penconazole (PEN)-induced oxidative stress in the cardiac tissue of adult rats. Male Wistar rats were divided into four groups of six each. The first group represented the controls. For the second group (PEN), no treatment was performed during the first 6 days, and then, the rats received intraperitoneally 67 mg/kg body weight (bw) of PEN every 2 days from day 7 until day 15, the sacrifice day. For the third group (Se + PEN), Se was administered daily through the diet at a dose of 0.5 mg/kg of diet for 15 days. Rats of this group received also every 2 days PEN (67 mg/kg bw) from day 7 until day 15. The fourth group (Se) received daily, through the diet, Se (0.5 mg/Kg of diet) during 15 days. Our results showed that Se reduced significantly the elevated cardiac levels of malondialdehyde and protein carbonyl following PEN treatment, and attenuated DNA fragmentation induced by this fungicide. In addition, Se modulated the alterations of antioxidant status: enzymatic (superoxide dismutase, glutathione peroxidase, and catalase) and nonenzymatic (glutathione and vitamin C) antioxidants in the heart of PEN-treated rats. This trace element was also able to alleviate perturbations of lipid profile. The protective effect of selenium was further evident through the histopathological changes produced by PEN in the heart tissue. Taken together, our results indicated that Se might be beneficial against PEN-induced cardiac oxidative damage in rats.