Mohamed Salah Allagui

Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by open fields, elevated plus maze and Radial 8-arms maze tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS).

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

Chronic lithium administration triggers an over-expression of GRP94 stress protein isoforms in mouse liver

Moderate doses of lithium were chronically administered to mice in order to verify whether the cytoprotective effects of lithium could be in part attributed to a molecular protection conferred by stress proteins/chaperones accumulation. In order to reach serum lithium levels within the common therapeutic values, mice were fed for 6 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.5 and 0.9 mM Li, respectively. Under these experimental conditions, no clinical side-effects were observed. Urea and creatinine concentrations in serum, lipids peroxidation level and activities of catalase, superoxide-dismutase and glutathione-peroxidase in liver and kidney were not significantly different from control values. Although the expression level of the constitutive HSP73 was not significantly modified, HSP72 was found to be down-regulated in kidney after 1 month. In liver, three protein bands were immunodetected by the anti-GRP94 antibody: 98 kDa and 96 kDa proteins corresponding to more or less glycosylated forms and/or phosphorylated forms of GRP94 and a 80 kDa protein probably being a cleavage product of GRP94. The 96 kDa and 80 kDa proteins were significantly up-regulated in liver of lithium-treated mice as compared to controls.

Effects of Rhus tripartitum fruit extract on CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats

Rhus tripartitum D.C., Anacardiaceae, has traditionally been used in Tunisia against many illnesses. The present study investigates, for the first time, the protective effects of the methanol extract of Rhus tripartitum fruit (MERT) against CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicty in Wistar rats. ALT, AST, LDH, GGT, creatinin, urea, and uric acid levels were studied. The changes in antioxidant parameters such as malondialdehyde (MDA) and protein carbonyl contents were also determined. The increased levels of MDA (30.97 and 11.50 nmol MDA/mg protein in liver and kidney, respectively) and protein carbonyls (13.4 and 17.95 nmol/mg protein in liver and kidney, respectively) were attenuated by MERT pretreatment (19.35 and 6.1 nmol MDA/mg protein and 9.15 and 12 nmol/mg protein in liver and kidney, respectively). The MERT pretreatment significantly reduced the increased biochemical parameters of liver and kidney caused by CCl4 and cisplatin treatment. The histopathologic observation showed that MERT pretreatment restores the altered tissues. The observed results could be due to the high phenolic content and to MERTs important antioxidant potential. This study supports the hepatoprotective and nephroprotective effects of R. tripartitum.

Impact of dietary restriction on peroxidative effects of nickel chloride in wistar rats.

ABSTRACT The purpose of this study, carried out in Wistar rats, was to evaluate the protective effect of dietary restriction (performed by intermittent fasting) against oxidative stress induced by a low concentration of nickel chloride in kidney, liver, uterus, and ovary. Lipid peroxidation (TBARS), catalase activity, and the levels of vitamins E and A in the blood were investigated in rats feed for 1 month either daily (N) or 1 day over two (intermittent fasting, IF) and then injected (NNi, IFNi) or not with nickel chloride (30 μmoles/kg body weight/day) for 10 days. Ni induced a significant increase of TBARS in organs of N rats. Intermittent fasting alone or associated to nickel treatment did not result in TBARS change in IF and IFNi rats. Catalase activity levels were found to be similar in N and IF rats. In Ni-treated rats a transient increase of catalase activity appeared at day 1 in the kidney and days 1 and 3 in the liver. Then, catalase activity was found to be inhibited until day 10. In the uterus and ovary, catalase activity was always found to be inhibited. In IFNi rats, no significant increase of catalase activity was observed as compared to IF rats. Vitamin E was inhibited from the 1st to the 10th day in Ni rats, whereas no significant changes were noted in IFNi rats. A moderate decrease of vitamin A was only found at days 1 and 3 in Ni rats. In conclusion, intermittent fasting is able to protect from oxidative stress induced by low concentration of Ni, but catalase and Vitamins E and A do not seem to be involved.

In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney

Abstract The present study investigated the in vitro and the in vivo antioxidant capacities of Allium sativum (garlic) extract against deltamethrin-induced oxidative damage in rat’s brain and kidney. The in vitro result showed that highest extraction yield was achieved with methanol (20.08%). Among the tested extracts, the methanol extract exhibited the highest total phenolic, flavonoids contents and antioxidant activity. The in vivo results showed that deltamethrin treatment caused an increase of the acetylcholinesterase level (AChE) in brain and plasma, the brain and kidney conjugated dienes and lipid peroxidation (LPO) levels as compared to control group. The antioxidant enzymes results showed that deltamethrin treatment induced a significantly decrease (pu2009<u20090.01) in brain and kidney antioxidant enzymes as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) to control group. The co-administration of garlic extract reduced the toxic effects in brain and kidney tissues induced by deltamethrin.

Syzygium Aromaticum Alleviates Cerium Chloride-Induced Neurotoxic Effect In The Adult Mice

Abstract Previous studies have brought to light the toxic effect of cerium chloride (CeCl3) but very little is known about the oxidative brain injury caused by this metal. Medical plants have a well-recognized role in the management of damage caused by pollutants such as CeCl3. Syzygium aromaticum, a potent natural source of bioactive compounds and rich in secondary metabolites, has a broad range of biological functions. The aim of this study is to investigate the capacity of Syzygium aromaticum ethanol extract (ESA) to improve the adverse effects of CeCl3 in the brain tissue. Adult mice were exposed to CeCl3 (20u2009mg/kg body weight [BW]), with or without ESA, for 60u2009days. We investigate mice’s behavior, damages of cholinergic system and oxidative stress parameters in mice brain. In the present study, in vitro test confirmed that ESA has antioxidant capacity attributed to the presence of flavonoids, polyphenols, and tannins contents. In vivo study showed that CeCl3 caused brain injuries manifested in memory impairment, increase in acetylcholinesterase activity, oxidative stress biomarkers (lipid, proteins, enzymatic and non-enzymatic antioxidant systems), and histopathological alteration in brain tissue. Addition of ESA repaired memory impairment, decreased acetylcholinesterase activity, restored oxidative state, and prevented histopathological alteration. In conclusion, the experimental results showed the protective effects of ethanol extract of Syzygium aromaticum against cerium-induced brain damage.

Chemical Composition and Antioxidant, Analgesic, and Anti-Inflammatory Effects of Methanolic Extract of Euphorbia retusa in Mice

Plants provide an alternative source to manage different human disorders due to various metabolites. The aim of this study is to investigate the phytochemical constituents of the methanolic extracts of Euphorbia retusa and to evaluate their antioxidant, anti-inflammatory, and analgesic activities. The phytochemical results obtained by HPLC and by chemical assay reactions have revealed the richness of the methanolic extract of E. retusa in active compounds, in particular polyphenols, flavonoids, and tannins. The methanolic extract shows significant antioxidant activities in vitro, in the DPPH and the FRAP assays. The antinociceptive activity was evaluated using acetic acid and hot-plate models of pain in mice. The anti-inflammatory activity was evaluated by carrageenan-induced paw edema. Oral pretreatment with the methanolic extract of E. retusa (200u2009mg/kg) exhibited a significant inhibition of pain induced either by acetic acid or by the heating plate and in a manner comparable to the standard drug paracetamol. E. retusa significantly reduced paw edema starting from the 3rd hour after carrageenan administration by increasing the activity of antioxidant enzymes (SOD, CAT, and GPx) in liver and paw tissues and decreasing the levels of MDA. These results may confirm the interesting potential of this plant as a treatment of various inflammatory and pain diseases.

Protective effects of Curcuma longa against neurobehavioral and neurochemical damage caused by cerium chloride in mice

Cerium chloride (CeCl3) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl3, 20xa0mg/kg BW) along with Curcuma longa extract, administrated by gavage (100xa0mg/kg BW), into mice for 60xa0days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl3-treated mice. In addition, CeCl3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl3-treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl3-induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl3-damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl3-induced damage in the brain.

Protective effect of Chaetomorpha gracilis aqueous extract against erythrocytes oxidative damage induced by high fat diet in treated mice

Abstract High fat diet (HFD) exposure is associated with various pathological dysfunctions, including haematological disorders and oxidative stress. The in vitro analysis of AECG revealed the presence of important levels of polyphenols and flavonoids, and denoted antioxidant capacities confirmed by nitric oxide radical (NO•), reducing the power and HPLC chemical components’ determinations. The animals exposed to HFD revealed a severe damage in the blood cells structure and haematological parameters accompanied with a significant decrease in serum Mg2+ and Ca2+ ATPase activities. Furthermore, malondialdehyde (MDA) and the advanced oxidation of protein products (AOPP) levels were significantly increased, while vitamin C level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were markedly reduced in the erythrocytes and platelets of HFD-treated mice. However, the co-administration of AECG with HFD-treated animals restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Chaetomorpha gracilis extract was a useful element preventing HFD-induced blood cells damage.