Publications Internationales

2022
Salah I, Adjroud O, Elwej A. Protective Effects of Selenium and Zinc Against Nickel Chloride-Induced Hormonal Changes and Oxidative Damage in Thyroid of Pregnant Rats. Biological Trace Element Research [Internet]. 2022;200 (5) :2183-2194. Publisher's VersionAbstract

Nickel chloride (NiCl2) is a heavy metal that may affect the function of the thyroid. Selenium (Se) and zinc (Zn) are essential trace elements involved in thyroid hormone metabolism. However, little is reported about thyrotoxicity during gestation. The current study aimed to investigate the protective effects of selenium and zinc against NiCl2-induced thyrotoxicity in pregnant Wistar rats. Female rats were treated subcutaneously (s.c.) on the 3rd day of pregnancy, with NaCl 0.9% and served as control, NiCl2 (100 mg/kg body weight (BW)) alone, or in association with Se (0.3 mg/kg, s.c.), ZnCl2 (20 mg/kg, s.c.), or both of them simultaneously. Oxidative stress parameters, thyroid biomarkers, and histopathological examination were evaluated. Results showed that NiCl2 exposure caused a significant decrease in maternal body weight and an increase in absolute and relative thyroid weight compared to the controls. NiCl2 administration also led to decreased plasma triiodothyronine (T3) and thyroxine (T4) with a concomitant significant increase in thyroid-stimulating hormone (TSH) levels when compared to that of control. In addition, an overall pro-oxidant effect was associated with a decrease in the reduced glutathione (GSH) and nonprotein thiol (NPSH) contents and the enzymatic activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and an increase in malondialdehyde (MDA). These biochemical disturbances were confirmed by histological changes. However, the co-treatment of Se and/or ZnCl2 attenuates NiCl2-induced changes. Our findings suggested that Se and ZnCl2 ameliorated NiCl2-induced thyrotoxicity in pregnant Wistar rats by exhibiting antioxidant effects.

Fedala A, Adjroud O, Bennoune O, Abid-Essefi S, Foughalia A, Timoumi R. Nephroprotective Efficacy of Selenium and Zinc Against Potassium Dichromate-Induced Renal Toxicity in Pregnant Wistar Albino Rats. Biological Trace Element Research [Internet]. 2022;200 (11) :4782-4794. Publisher's VersionAbstract

Hexavalent chromium (CrVI) compounds are potent toxicants commonly used in numerous industries. Thus, potential toxic effects and health hazards are of high relevance. Selenium (Se) and zinc (Zn) are known for their antioxidant and chemoprotective properties. However, little is known about their protective effects against CrVI-induced renal damage during pregnancy. In this context, the present study aimed to investigate the protective efficacy of these two essential elements against potassium dichromate-induced nephrotoxicity in pregnant Wistar Albino rats. Female rats were divided into control and four treated groups of six each receiving subcutaneously on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg, s.c. single dose) alone, or in association with Se (0.3 mg/kg, s.c. single dose), ZnCl2 (20 mg/kg, s.c. single dose) or both of them simultaneously. The nephrotoxic effects were monitored by the evaluation of plasma renal parameters, oxidative stress biomarkers, DNA damage, and renal Cr content. The obtained results showed that K2Cr2O7 disturbed renal biochemical markers, induced oxidative stress and DNA fragmentation in kidney tissues, and altered renal histoarchitecture. The co-administration of Se and/or ZnCl2 has exhibited pronounced chelative, antioxidant, and genoprotective effects against K2Cr2O7-induced renal damage and attenuated partially the histopathological alterations. These results suggest that Se and Zn can be used as efficient nephroprotective agents against K2Cr2O7-induced toxicity in pregnant Wistar Albino rats.

2021
Sengouga D, Adjroud O, Salah I, Fedala A. CHROMIUM TOXICITY ON THE ELECTROLYTE BALANCE AND ADRENAL HISTOLOGY IN WISTAR MALE RATS.  Nutr.Santé. 2021;10 (1).
Fedala A, OUNASSA ADJROUD, Saouli A, Imane S. ZINC ALLEVIATES POTASSIUM DICHROMATE-INDUCED HEPATOTOXICITY IN PREGNANT WISTAR RATS. Malaysian Journal Of Biochemistry & Molecular Biology . 2021;2 :10-16 .Abstract

The present study aimed to investigate the potential protective effects of zinc (Zn) against hexavalent chromium-induced hepatotoxicity in pregnant Wistar rats. Female rats were treated subcutaneously (s.c) on the 3 rd day of pregnancy, with NaCl 0.9 % and served as control, K₂Cr₂O7 (10 mg/kg bw) alone, or K₂Cr₂O7 in association with ZnCl2 (20 mg/kg bw). Hepatic biochemical parameters, oxidative stress biomarkers and DNA damage were monitored. Results revealed that K₂Cr₂O7 disturbed plasma ALT, AST, ALP and GGT, induced hepatic oxidative stress and DNA fragmentation. The co-treatment with Zn has alleviated K2Cr2O7-induced hepatotoxicity by exhibiting antioxidant and genoprotective effects in pregnant Wistar rats.

Fedala A, Adjroud O, Abid-Essefi S, Timoumi R. Protective effects of selenium and zinc against potassium dichromate–induced thyroid disruption, oxidative stress, and DNA damage in pregnant Wistar rats. Environmental Science and Pollution Research. 2021;28 :22563–22576.Abstract

Hexavalent chromium (CrVI) is an environmental pollutant and an endocrine-disrupting metal. Se and Zn are essential trace elements, known to play a crucial role in thyroid homeostasis. However, there is a lack of data reporting thyrotoxicity during gestation. In this study, we investigated the protective effects of selenium and zinc against potassium dichromate–induced thyrotoxicity in pregnant Wistar rats. Thirty pregnant Wistar rats were divided into control and four treated groups receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg, s.c) alone, or in association with Se (0.3 mg/kg, s.c), ZnCl2 (20 mg/kg, s.c), or both of them simultaneously. The hormonal profile, oxidative stress biomarkers, DNA damage, and histological modifications were evaluated. Our main findings showed that K2Cr2O7 promoted hypothyroidism, oxidative stress, genotoxicity, and histological alterations in the thyroid gland. The co-treatment with Se or ZnCl2 has mitigated K2Cr2O7-induced thyrotoxicity in pregnant Wistar rats by exhibiting antioxidant and genoprotective effects. However, the combined co-treatment of both of them was less thyroprotective, and therefore, further investigations on the synergetic interaction of Se and Zn against CrVI toxicity using different doses and exposure routes are required.

Salah I, Adjroud O, Elwej A. Protective Effects of Selenium and Zinc Against Nickel Chloride–Induced Hormonal Changes and Oxidative Damage in Thyroid of Pregnant Rats. Biological Trace Element Research . 2021;155.Abstract

Nickel chloride (NiCl2) is a heavy metal that may affect the function of the thyroid. Selenium (Se) and zinc (Zn) are essential trace elements involved in thyroid hormone metabolism. However, little is reported about thyrotoxicity during gestation. The current study aimed to investigate the protective effects of selenium and zinc against NiCl2-induced thyrotoxicity in pregnant Wistar rats. Female rats were treated subcutaneously (s.c.) on the 3rd day of pregnancy, with NaCl 0.9% and served as control, NiCl2 (100 mg/kg body weight (BW)) alone, or in association with Se (0.3 mg/kg, s.c.), ZnCl2 (20 mg/kg, s.c.), or both of them simultaneously. Oxidative stress parameters, thyroid biomarkers, and histopathological examination were evaluated. Results showed that NiCl2 exposure caused a significant decrease in maternal body weight and an increase in absolute and relative thyroid weight compared to the controls. NiCl2 administration also led to decreased plasma triiodothyronine (T3) and thyroxine (T4) with a concomitant significant increase in thyroid-stimulating hormone (TSH) levels when compared to that of control. In addition, an overall pro-oxidant effect was associated with a decrease in the reduced glutathione (GSH) and nonprotein thiol (NPSH) contents and the enzymatic activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and an increase in malondialdehyde (MDA). These biochemical disturbances were confirmed by histological changes. However, the co-treatment of Se and/or ZnCl2 attenuates NiCl2-induced changes. Our findings suggested that Se and ZnCl2 ameliorated NiCl2-induced thyrotoxicity in pregnant Wistar rats by exhibiting antioxidant effects.

2020
Salah I, Adjroud O, Fedala A, Saouli A. Potential Protective Effects of Selenium and Zinc against Thyroid Toxicity Induced by Nickel in Preimplanted Wistar Albino Rats. Toxicology International [Internet]. 2020;26 (1) :54–63. Publisher's VersionAbstract

Nickel Is A Heavy Metal That May Affect The Function Of The Thyroid. The Present Study Was Undertaken To Assess The Protective Effects Of Selenium And Zinc Against Nickel-induced Thyrotoxicity In Preimplanted Wistar Albino Rats. Nickel Is Administered Alone (100 Mg/kg Body Weight) Subcutaneously Or In Combination With Selenium (0.3 Mg/kg Body Weight) Either With Zinc (20 Mg/kg Body Weight) Or Combined With Both Selenium And Zinc. All Groups Of Rats Were Injected On Day 3 Of Gestation In The Pre-implantation Period. Exposure Of Rats To Nickel Caused A Significant Decrease In Maternal Body Weight On Days 6 And 20 Of Gestation And An Increase In Absolute And Relative Thyroid Weight Compared To The Controls. Nickel Treatment Was Also Led In Decreased Plasma Triiodothyronine, Thyroxine With A Concomitant Significant Increase In Thyroid-stimulating Hormone Levels When Compared To Control. These Changes Were Confirmed By Histological Damages. However, Co-administration Of Selenium And/or Zinc To Nickel-treated Rats Restored The Hormonal And Histological Aspects. Our Findings Suggested That Selenium And Zinc Ameliorated Nickel Induced Thyroid Damage.

BOULILA I, Adjroud O. PROTECTIVE EFFECTS OF SELENIUM AND ZINC ON NICKEL CHLORIDE INDUCED REPRODUCTIVE TOXICITY IN WISTAR ALBINOS PREIMPLANTED RATS. Studia Universitatis Vasile Goldis Seria Stiintele Vietii (Life Sciences ) . 2020;30 (3) :126 - 135.Abstract

: The aim of this study was to investigate that nickel chloride (NiCl2) induced reproductive toxicity in pre- implanted Wistar Rats and examined the possible protective effect of zinc chloride and selenium on plasma concentration of the hormones of 17 b etradiol (E2) and progesterone (prog); on the reproductive organ’s histology and on development. Experimental results showed the subcutaneous (s.c) administration of Nicl2 to Wistar albino Rats induced a decrease in plasma concentration of E2 and prog in addition, disturbance in development parameters and structural damages to the histology of the reproductive organs. Conversely, Se and ZnCl2 dues to the antioxidants property, regulate the secretion of E2 and Prog hormones, prevent alterations in the reproductive organs and in development in preimplanted rates receiving NiCl2.

2015
OUNASSA ADJROUD. Nephroprotective Effects of Selenium against Nickel Chloride-Induced Nephrotoxicity in Pregnant Rats. International Proceeding of Chemical, Biological & Environment. 2015.
2013
Adjroud O. The toxic effects of nickel chloride on liver, erythropoiesis, and development in Wistar albino preimplanted rats can be reversed with selenium pretreatment. Environmental toxicology. 2013;28 (5) :290-298.Abstract

The exposure to nickel chloride (NiCl2) can cause hematotoxicity and hepatotoxicity and canaffect development. The present study pertains to the protective effect of selenium (Se) against NiCl2-induced toxicity in preimplanted Wistar albino rats. The subcutaneous (s.c.) administration of 25 or 50 mg/kg of NiCl2 to Wistar albino rats on day 3 of gestation induced an immediate and significant decrease in maternal body weight and anemia 2 days after treatment. In addition, an increase in plasma aspartate aminotransferase (AST) was observed. These effects were maintained on day 20 of gestation. Moreover, a significant increase in plasma alanine aminotransferase (ALT) levels was observed with the administration of 25 mg/kg of NiCl2. Conversely, administration of 50 mg/kg of NiCl2 by s.c. injection increased erythropoiesis at day 20 of gestation and decreased platelets counts. In addition, administration of 100 mg/kg of NiCl2 markedly reduced the maternal body weight and number of live fetuses and increased fetal loss, predominantly at the end of the experimental period. All dose levels of NiCl2 caused an alteration in the hepatic histoarchitecture. When 0.3-mg/kg Se was injected s.c. with 100-mg/kg NiCl2, the levels of plasma AST and ALT and the structure of the liver were restored. Administration of 20 mg/L/day of NiCl2 in the drinking water significantly reduced the maternal body weight at day five of gestation as well as erythropoiesis during the exposure period. The present study suggests that Se can counteract the nocuous effect of nickel on the liver; however this antioxidant did not prevent alterations in development and erythropoiesis. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.

2010
Adjroud O. Protective effects of selenium against potassium dichromate-induced hematotoxicity in female and male Wistar albino rats. Annales de Toxicologie Analytique [Internet]. 2010;22 (4) :165-172. Publisher's VersionAbstract

Objective: Potassium dichromate (K2Cr2O7) is a potent pollutant for human and animal health. The purpose of the current work is to compare the effect of K2Cr2O7 using variations in the dose, route of administration and duration of exposure in male and female Wistar albino rats and to research the interaction of chromium and selenium with a special focus on hematopoiesis. 

Materials and methods: K2Cr2O7 was subcutaneously administered alone (10, 50 and 100 mg/kg body weight) or K2Cr2O7 (10 mg/kg) in association with selenium (0.3 mg/kg) was administered to female Wistar albino rats. Male rats received in their drinking water K2Cr2O7 (30 mg/L/day) alone or in association with Se (0.3 mg/L/day) for 20 consecutive days. The hematological parameters were evaluated on days 3, 6 and 21 after subcutaneous (sc.) treatment in female rats and on days 10 and 20 after oral administration in male rats. 

Results: K2Cr2O7− induced during the first three days a significant (p < 0.05) dose-dependent decrease in the number of erythrocytes, platelets, leucocytes, lymphocytes and the hematocrit levels, and a dose-dependent increase in the number of granulocytes and monocytes. In the drinking water, chromium sc. significantly decreased the number of leucocytes and lymphocytes on day 10 after treatment and elevated the number of granulocytes and monocytes 20 days later. Selenium sc. counterbalanced the hematotoxic effects of chromium in female rats. 

Conclusion: These results suggest that the selenium has a protective role against the hematotoxicity of subcutaneous chromium in female Wistar rats.

2009
Adjroud O. Effects of potassium dichromate on haematological. parameters in female and male Wistar albino RATS. Ass. Univ. Bull. Environ. Res [Internet]. 2009;12 (2) :87-98. Publisher's VersionAbstract

Hexavalent chromium is a potent toxic agent. It has been found to be carcinogenic in human and animal. The purpose of the current work is to compare the effect of potassium dichromate (K2Cr2O7) using variations in the dose, route of administration, and duration of exposure in male and female wistar albino rats with special focus on hematological parameters. K2Cr2O7 was administered either in the drinking water with a dose of 30 mg/l for 20 consecutive days to male wistar albino rats, or as a single dose subcutaneously (s.c) at 10, 50 and 100 mg/Kg body weight (b w) to female wistar albino rats. Control groups received NaCl 0.9% (0.3 ml s.c), or drinking distilled water. Haematological parameters were recorded on day 3, 6, and 21 after subcutaneous exposure, or on day 10 and 20 after oral treatment. 10 mg/Kg b w of K2Cr2O7 given subcutaneously induced during the first three days a marked decrease in the number of erythrocytes (-6%) of leucocytes (-30%) of platelets (-48%) and of hematocrit values (-15%), while the number of granulocytes is augmented (+124%) in comparison with control. Hemoglobin concentration and lymphocyte counts decreased markedly on day 6 after exposure. Chromium 50 mg/Kg b w, s.c mainly affected during the first three days the leucopoietic indices inducing leucopoenia (-55%), lymphopoenia
(-57%), monocytosis (+104%), granulocytosis (+204%), and thrombocytosis (+38%) if compared with control, while the erythrocytic counts and hemoglobin concentration decreased from day 6 (-22%) and (-21%) respectively until day 21 (-41%) and (-36%) respectively, and hematocrit values decreased at the end of experiment (-36%) in comparison with control. The higher dose of chromium (100 mg/Kg b w, s.c) reduced during the first three days the number of erythrocytes (-20%), platelets (-20%), total leucocytes (-55%), lymphocytes (-59%) and augmented the number of monocytes (+56 %), and granulocytes (+166%), while on day 6 the number of platelets augmented (+27%) in comparison with control. In drinking water, 30 mg/l of chromium given to male wistar albino rats had no effect on all erythropoietic parameters studied with the exception of the elevation (+21%) in platelet counts at the end of exposure, while the number of lymphocytes and total leucocytes were significantly reduced on day 20 after exposure (-37%) and (-37%) respectively. Conversely, the number of granulocytes and monocytes markedly increased on day 10 after exposure (+42%) and (+22%) respectively if compared with control. Short-term exposures to low dose of K2Cr2O7, s.c induce in female wistar albino rats erythrocytopenia, thrombocytopenia, leucopoenia, lymphopaenia, granulocytosis, monocytosis, and a decrease in hematocrit values and hemoglobin concentration while in drinking water chromium was susceptible to affect in male rats the immune response inducing leucopoenia, lymphopoenia, monocytosis, and granulocytosis, while this oral route of exposure had no effect on erythropoietic parameters.

Adjroud O, MOUFFOK S. EFFECTS OF NICKEL CHLORIDE ON HEMATOLOGICAL AND DEVELOPMENTAL PARAMETERS IN Wistar albino PREGNANT RATS. Ass. Univ. Bull. Environ. Res [Internet]. 2009;12 (1). Publisher's VersionAbstract

Several reports have suggested that soluble salts nickel may affect on hematopoiesis and development. In this study female Wistar albino rats (180-300g) received NiCl2, 6H2 O, subcutaneously (25, 50 and 100 mg/kg body weight (b w) or in drinking water (20 mg/100 ml). Selenium (0.3 mg/kg b w, s.c.) was combined to NiCl2 (100 mg/kg b w, s.c.). Control groups received NaCl 0.9% (0.3 ml s.c) or drinking distilled water. All groups of rats were injected on day 4 of pregnancy in pre-implantation period. Haematological parameters were recorded on day 6 and 21 of pregnancy. Developmental parameters were assessed on day 21 of pregnancy. 25 mg/kg b w, of NiCl2 s.c, induced on day 6 an immediate and significant decrease in erythrocyte counts, hematocrit values, and haemoglobin concentrations. This depletion was maintained on day 21 of pregnancy compared to control values.On other hand 50 mg/k b w, NiCl2, s.c, reduced on day 6 of pregnancy the erythrocyte counts, hematocrit values and platelets counts. Inversely, on day 21 this dose elevated the erythrocyte counts, hematocrit values and haemoglobin concentrations ,with depletion of the platelets counts compared to control values. In group introduced 100 mg/kg b w, of NiCl2, s.c had no effect on all haematological parameters studied. NiCl2, significantly reduced the maternal body weight on day 6 and 21 of pregnancy in a dose – dependent manner in rats treated subcutaneously and in drinking water compared with control values. NiCl2, s.c. (100 mg/kg b w) markedly reduced the number of live fetuses and elevated the number of abortions on day 21 of pregnancy compared to control values. NiCl2, s.c or in drinking water had no effect on fetal body weight. Selenium (0.3 mg/kg b w, s.c.) combined to NiCl2 (100 mg/kg b w, s.c.) did not improve the effect of NiCl2.

1995
Adjroud O. Peripheral excitatory effects of two enkephalinase inhibitors, acetorphan and thiorphan, and an enkephalin analogue, [d-Ala2–Met5]-enkephalinamide, on uterine motility in periparturient rats in vivo and in vitro. Journal for Reproduction and Fertility [Internet]. 1995;104 (2) :181–186 . Publisher's VersionAbstract

The effects of two enkephalinase inhibitors, acetorphan and thiorphan, and the enkephalin analogue [d-Ala2\p=n-\Met5]-enkephalinamide (DAMEA), on spontaneous uterine contractions were studied at day 21 of pregnancy in rats following treatment in vivo or in vitro. Acetorphan (10 mg kg\m=-\1)and thiorphan (1 mg kg\m=-\1),immediately after their i.v. administration, increased the duration of spontaneous contractions 3.4- and 4.6-fold, respectively, but did not modify the maximum amplitude. Similarly, thiorphan (40 \g=m\moll\m=-\1) increased the duration of contractions when administered in vitro. Thiorphan was ineffective during the first 30 min when given into the cerebral ventricles (50 \g=m\gper rat). These results suggest that the enkephalinase inhibitors are acting via a peripheral opioid pathway; and this conclusion is supported by the observation that thiorphan potentiated the stimulatory effect of a submaximal dose of DAMEA administered in vitro. The excitatory effects of DAMEA and the enkephalinase inhibitors were blocked by naloxone. This antagonistic effect of naloxone on uterine motility in the periparturient rat uterus, induced by either acetorphan and thiorphan or DAMEA, seems to be regulated by peripheral opiate receptors. Naloxone (10 mg kg\m=-\1 s.c.) increased both the amplitude and duration of uterine motility in vivo; however, naloxone (26 \g=m\moll\m=-\1 and 52 \g=m\moll\m=-\1) produced a paradoxical dose-dependent biphasic effect in vitro.

1988
Clabaut M, Duclos R, Chartrel N, Adjroud O, Acritopoulou-Fourcroy S, Collado H, Schrub JC. Variation of myometrial activities and steroid sexual hormones following bilateral ovariectomy in the rat at midpregnancy. Acta Physiol Hung [Internet]. 1988;71 (4) :477-83. Publisher's VersionAbstract

The effects of bilateral ovariectomy on uterine motility and levels of progesterone, oestradiol, cAMP, adrenaline and PGF2 alpha were studied in the rat at midpregnancy. Animals were randomly divided into two groups, at least 15 rats in each, sham-operated serving as controls and ovariectomized. The spontaneous uterine mechanical activity of Wistar rats was recorded isometrically and the electrical activities were recorded simultaneously by two bipolar electrodes. Within 30 minutes of ovariectomy a significant increase of the amplitude of uterine contractions was observed and the simultaneity of electrical activity was significantly improved; these effects became more pronounced at 1h post-ovariectomy (p less than 0.005). Plasma progesterone levels decreased by 20% (p less than 0.01) at 30 min and by 50% (p less than 0.001) 1h after ovariectomy, whereas oestrogen levels remained unchanged. Levels of adrenaline, cAMP and PGF2 alpha in the uterine tissue 1h following ovariectomy were affected as follows: adrenaline (p less than 0.05) and cAMP (p less than 0.001) were reduced and PGF2 alpha augmented (p less than 0.05). It appears that variation of the ratio oestrogens/progesterone induces precociously the activation of uterine mobility and exerts an effect on some factors involved in the regulation of the rat myometrium at midpregnancy.