Protective Effect Of Α-lipoic Acid Research Articles

Potential protective effect of alpha lipoic acid against testicular oxidative stress and altered gene expression induced by gentamicin treatment

Background: Gentamicin induces testicular damage in association with oxidative stress explained by different mechanisms, including gene expression suppression of some antioxidant enzymes. The aim of the study: To investigate the potential protective effects of α-lipoic acid against gentamicininduced testicular oxidative stress in terms of altered gene expression. Materials and methods: A parallel experimental study was conducted including fifty adult male albino rats. The animals were grouped into five. The control group received intraperitoneal NaCl 0.9%, while the other groups received 36.5mg/kg/day intraperitoneal gentamicin. Group-1 received gentamicin only, group-2 received gentamicin + intraperitoneal α-lipoic acid 100mg/kg/day, group-3 received gentamicin + intraperitoneal α-lipoic acid 200mg/kg/day, and group-4 received gentamicin + oral vitamin E 100mg/kg/day. All treatments were given for 14 days. The animals were euthanized in two halves on the 15th and 60th days. Testes were immediately removed, frozen, and evaluated for oxidative stress biomarkers and gene expression of antioxidant enzymes. Results: Gentamicin increased malondialdehyde by mean difference ± standard error of 115.57 ± 2.18, decreased total antioxidant capacity by -9.23 ± 0.27, and decreased catalase and superoxide dismutase activities by -1.89 ± 0.45 and -11.77 ± 2.86, respectively, compared to the control. Additionally, gentamicin downregulated gene expression of catalase, glutathione peroxidase, and superoxide dismutase. However, adding vitamin E or α-lipoic acid cured the oxidative stress and partially to completely upregulated the gene expression. Conclusion: Reversal of testicular oxidative and gene suppression associated with gentamicin could be achieved with α-lipoic acid co-treatment, which might be applied in human studies.

Hepatic-Metabolic Activity of α-Lipoic Acid-Its Influence on Sphingolipid Metabolism and PI3K/Akt/mTOR Pathway in a Rat Model of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration.

The Effect of Alpha-Lipoic Acid against Methotrexate on Testicular Damage in Rats

Aim: The toxic effects of methotrexate, a chemotherapeutic, on the testicles is an important side effect. Methotrexate impairs spermatogenesis and fertility and causes oligospermia. In this study, we aimed to minimize the testicular toxicity, those being the side effects of methotrexate, by using the probable protective effects of α-lipoic acid, a potent antioxidant.
 Materials and Methods: Twenty-eight male Sprague Dawley rats that we employed in this research were separated into three groups as control (0.09% PS) (n=8), methotrexate (20 mg/kg) (n= 10), and methotrexate (20 mg/kg) + α-lipoic acid (100 mg/kg) (n= 10). We performed a histochemical analysis on the testicular tissue of rats using hematoxylin-eosin and Masson’s trichrome. We performed an immunohistochemical analysis using inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) primer ab.
 Results: The histochemical evaluation revealed a significant decrease in the methotrexate-induced testicular toxicity in the α-lipoic acid-treated groups. On the other hand, TNF-α and iNOS immunostaining results were also observed to support these results.
 Conclusion: The treatment use of α-lipoic acid succeeded in protecting against methotrexate-induced testicular damage through an α-lipoic acid-mediated antioxidant and anti-inflammatory mechanisms. α-lipoic acid can be used in combination with methotrexate as a protector against side effects during anticancer therapy. In the present study, it was shown that α-lipoic acid can be used in combination with methotrexate as a protector against side effects during anticancer treatment.

Alpha-lipoic acid inhibits sodium arsenite-mediated autophagic death of rat insulinoma cells.

To investigate the protective effect of α-lipoic acid on sodium arsenite (NaAsO2) induced INS-1 cells injury and its mechanism. The cell viability was measured by CCK-8 assay. The autophagosomes was observed under transmission electron microscopy. The autophagosomes in cells transfected with green fluorescent protein microtubule-associated protein light chain 3 (GFP-LC3) plasmids were observed under a laser scanning con-focal microscope. The expression of LC3-II, P62, PI3K, and mTOR proteins in INS-1 cells treated with a combination of chloroquine (CQ, autophagy inhibitor) and NaAsO2 were detected by Western blot assay. The expression of LC3-II, P62, PI3K, and mTOR proteins were detected in INS-1 cells treated with a combination of rapamycin (autophagy inducer, mTOR inhibitor) and α-LA. The cytotoxicity induced by NaAsO2 was reversed by α-LA, and the viability of NaAsO2-treated INS-1 cells increased. α-LA pretreatment decreased the autophagosome accumulation induced by NaAsO2. α-LA also reduced the fluorescence spot aggregation of GFP-LC3 in INS-1 cells exposed to NaAsO2 as observed under a laser scanning con-focal microscope. α-LA inhibited NaAsO2 induced autophagy by up-regulating PI3K and mTOR and down-regulating LC3-II and P62. CQ inhibited NaAsO2 induced autophagy by up-regulating PI3K, mTOR, P62 and down-regulating LC3-II. α-LA inhibited rapamycin-induced autophagy by up-regulating PI3K, mTOR and P62 and down-regulating LC3-II. The results showed that NaAsO2 could induce autophagy activation in INS-1 cells. The α-LA may inhibit autophagy activation by regulating the PI3K/mTOR pathway. The data indicated that α-LA might inhibit the NaAsO2-induced autophagic death of INS-1 cells by regulating the PI3K/mTOR pathway.

α-Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis.

Fluoride is widely used in agricultural production and food packaging. Excessive fluoride in water and food is a serious threat to liver health. α-Lipoic acid, a natural free radical scavenger, has hepatoprotective properties. However, the protective effect of α-lipoic acid on fluorohepatotoxicity is uncertain. The aim of this study was to investigate the mechanism of ferroptosis in α-lipoic acid preventing fluoride-induced hepatotoxicity. Five-week-old ICR mice were treated with sodium fluoride (100 mg/L) and/or α-lipoic acid (200 mg/kg) for 9 weeks. The results showed that α-lipoic acid attenuated fluoride-induced damage to liver morphology and ultrastructure. Moreover, α-lipoic acid alleviated fluoride-induced iron accumulation, increased oxidative stress, and elevated lipid peroxidation in the liver. In addition, the mechanism study found that α-lipoic acid prevented fluoride-induced ferroptosis through the System Xc-/GPX4 axis, lipid peroxidation axis, and iron metabolism axis, but it was interestingly not regulated by mitochondrial free radical axis in the hepatocytes. Altogether, this study indicated that α-lipoic acid prevents fluoride-induced liver injury by inhibiting ferroptosis, which has potential implications for the prevention and treatment of fluoride-induced liver injury.

The Protective Effect of α-Lipoic Acid against Gold Nanoparticles (AuNPs)-Mediated Liver Damage Is Associated with Upregulating Nrf2 and Suppressing NF-κB.

This study examined if regulating the keap-1? Nrf2 antioxidant pathway mediated gold nanoparticles (AuNPs) induced liver damage, and examined the protective effect of co-supplement of α-lipoic acid (α-LA). Rats were separated into 4 groups (n = 8/each) as control, α-LA (200 mg/kg), AuNPs (5 µg/2.85 × 1011), and AuNPs (5 µg/2.85 × 1011) + α-LA (200 mg/kg). After 7 days, AuNPs induced severe degeneration in the livers of rats with the appearance of some fatty changes. In addition, it increased serum levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (ɣ-GTT), and aspartate aminotransferase (AST), as well as liver levels of malondialdehyde (MDA). Concomitantly, AuNPs significantly depleted hepatic levels of total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) but increased hepatic levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). It also reduced mRNA levels of B-cell lymphoma 2 (Bcl2) and heme oxygenase-1 (HO-1) but significantly increased those of Bax and cleaved caspase-3, as well as the ratio of Bax/Bcl2. In addition, AuNPs enhanced the total and nuclear levels of NF-κB p65 but reduced the mRNA and total and nuclear protein levels of Nrf2. Of note, AuNPs did not affect the mRNA levels of keap-1. All these events were reversed by α-LA in the AuNPs-treated rats. In conclusion, α-LA attenuated AuNPs-mediated liver damage in rats by suppressing oxidative stress and inflammation, effects that are associated with upregulation/activation of Nrf2.

Modulation of COX-2 and NADPH oxidase-4 by alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats

AimsThis study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats. Main methodsEighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR. Key findingsAdministration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4. SignificanceALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP–induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1β, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP–induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP–induced alterations in the neurological, immunological, and reproductive parameters.

Protective Effects of α-Lipoic Acid and Chlorogenic Acid on Cadmium-Induced Liver Injury in Three-Yellow Chickens.

Simple SummaryCadmium (Cd) exerts pernicious influences on global health. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting Cd toxicity in vivo in three-yellow chickens. Administration of Cd (50 mg/L) alone lowered the production performance and resulted in biochemical, histologic and enzyme changes within the liver consistent with hepatic injury induced by oxidative stress and apoptosis of hepatocytes. However, the above variations of the Cd group were partially or fully reversed by administration of either α-LA or CGA; their combination showed an even better effect in attenuating Cd-induced hepatotoxicity. This study provided a practical and feasible approach to rescuing Cd intoxication in animal production.Cadmium (Cd) is a type of noxious heavy metal that is distributed widely. It can severely injure the hepatocytes and cause liver dysfunction by inducing oxidative stress and mitochondrial damage. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting cadmium toxicity in vivo in three-yellow chickens. For three months, CdCl2 (50 mg/L) was administrated through their drinking water, α-LA (400 mg/kg) was added to feed and CGA (45 mg/kg) was employed by gavage. The administration of Cd led to variations in growth performance, biochemical markers (of the liver, kidney and heart), hematological parameters, liver histopathology (which suggested hepatic injury) and ultrastructure of hepatocytes. Some antioxidant enzymes and oxidative stress parameters showed significant differences in the Cd-exposure group when compared with the control group. The groups treated with Cd and administrated α-LA or CGA showed significant amelioration with inhibited mitochondrial pathway-induced apoptosis. Combining both drugs was the most effective in reducing Cd toxicity in the liver. In summary, the results demonstrated that α-LA and CGA may be beneficial in alleviating oxidative stress induced by oxygen free radicals and tissue injury resulting from Cd-triggered hepatotoxicity.

The protective effects of α-lipoic acid on fluoride-induced reproductive lesion in rats via oxidative stress-mediated endoplasmic reticulum stress

Objective: To determine the oxidative stress and endoplasmic reticulum stress and their changes after α-lipoic acid (α-LA) intervention, and to explore the effect and mechanism of fluoride-induced reproductive lesion. Methods: A total of 40 male Sprague-Dawley (SD) rats were randomly divided into four groups, control group(0.9% sodium chloride), α-LA group(100 mg/kg α-LA), NaF group(25 mg/kg NaF), and NaF+α-LA group(25 mg/kg NaF+100 mg/kg α-LA). Each group was treated in the way of intragastric administration for eight weeks. Sperm quality and the content of NaF in testis were analyzed. The morphologic changes of the testis were observed with the use of HE staining and the apoptosis was detected by the TUNEL assay. Biochemical method was used to measure oxidative stress. Western blot was used to detect the expression of endoplasmic reticulum stress markers, such as GRP78, PERK, and CHOP. Results: Compared with the control group, the NaF group had a low level in sperm density [(5.99±1.45)×10(6)/ml to (10.96±1.83)×10(6)/ml, P<0.01] and sperm vitality [(33.40±2.71)% vs (66.41±3.33)%, P<0.01], but a high level in sperm abnormality rate [(26.43±2.43)% vs (11.44±1.55)%, P<0.01]. Compared with the NaF group,the NaF+α-LA group had a high level in both sperm density [(8.47±0.82)×10(6)/ml vs (5.99±1.45)×10(6)/ml, P<0.05] and sperm vitality [(49.97±3.51)% vs (33.40±2.71)%, P<0.05], but a low level in sperm abnormality rate [(22.69±2.39)% vs (26.43±2.43)%, P<0.05].There was a significantly higher content of NaF in testis in the NaF group [(11.14±0.77) μg/g vs (5.78±0.28) μg/g, P<0.01] than the control group. Optical microscope was used to observe the morphologic changes of the testis, and it was showed that loose structure appeared both in spermatogenic cells and mature sperm cells while the amount of them decreased. However, after the administration of α-LA, there were complete organelles structure and exfoliated cells in the lumen ameliorated. TUNEL assay found that the apoptotic cells were in a high level in the NaF group [(61.32±7.14)% vs (6.99±2.17)%, P<0.01], while α-LA significantly suppressed the percentage of apoptotic cells in the NaF+α-LA group compared with the Naf group [(45.96±5.31)% vs (61.32±7.14)%, P<0.01].Oxidative stress assays showed that there were higher express of Malondialdehyde(MDA) content [(5.46±0.30) nmol/mgprot vs (3.24±0.58) nmol/mgprot, P<0.01], the activity of Superoxide Dismutase(SOD) [(6.04±0.71) U/mgprot vs (7.19±0.52) U/mgprot, P<0.01] and Glutathione peroxidase(GSH-Px) [(23.67±0.99) U/mgprot vs (26.91±1.67) U/mgprot, P<0.01] in the NaF group than the control group. To compared with the NaF group, the counterpart in the NaF+a-LA group of MDA content was less [(4.66±0.70) nmol/mgprot vs (5.46±0.30) nmol/mgprot, P<0.05] and the GSH-Px activity was high [(25.90±1.93) U/mgprot vs (23.67±0.99) U/mgprot, P<0.05]. Towards the detection of endoplasmic reticulum stress, we found that there were all in higher level in the NaF group that the expression of GRP78 [(0.79±0.05) vs (0.45±0.09), P<0.01], PERK [(0.71±0.04) vs (0.40±0.05), P<0.01], and CHOP[(0.79±0.09) vs (0.19±0.08), P<0.01] than the control group, and to compared with the NaF group, α-LA significantly supressed the expression of GRP78 [(0.46±0.06) vs (0.79±0.05), P<0.01] and CHOP[(0.52±0.09) vs (0.79±0.09), P<0.01]. Conclusion: α-lipoic acid plays a protective role in fluoride-induced reproductive lesion in rats by oxidative stress-mediated endoplasmic reticulum stress.

Protective Effects of α-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia.

The aim of the present study was to observe the protective effects of α-lipoic acid (ALA) on vascular injury in rats with hyperuricemia (HUA). The ALA treatment groups (10, 30 and 90 mg/kg, respectively) were administered with ALA via gavage for 2 weeks. Subsequently, the levels of blood urea nitrogen (BUN), creatinine (CREA), uric acid (UA), total cholesterol (TC), high density lipoprotein-C (HDL-C) and low density lipoprotein-C (LDL-C) were measured; the activities of glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and xanthine oxidase (XOD) were also determined. The thoracic aorta of rats in each experimental group was observed under a light microscope; ultrastructural analysis was performed. SOD and CAT protein contents were investigated by Western blotting. The results revealed that: i) Compared with the model group, the levels of UA were decreased in the ALA groups and the levels of BUN, CREA, TC, and LDL-C decreased in the 30 and 90 mg/kg ALA groups (P<0.05); ii) compared with the model group, the activities of GSH-Px, SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P&lt;0.05); and iii) in the model and 10 mg/kg ALA groups, edema and shedding were observed in endothelial cells. Compared with the model and 10 mg/kg ALA groups, the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells. In summary, the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes, which leads to endothelial cell damage and vascular lesions. ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.

Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling.

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation–induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.

Evaluation of therapeutic potentials of α-Lipoic acid versus stem cells-derived microvesicles against experimentally–induced gastric ulcer in adult Male Albino Rats (Light and Electron microscopic study)

Background: Alpha-Lipoic acid (ALA), is an antioxidant endogenous substance. It is available in small amounts in food. Mesenchymal stem cells (MSCs) derived microvesicles (MSC-MVs) have numerous paracrine protective effects against tissue injury that are mediated by inflammatory, apoptotic and oxidative stress. Aim of the Work: Our study was done to assess the protective effects of Alpha Lipoic Acid versus MSC-MVs on indomethacin-induced gastric ulcer in rats. Material and Methods: Forty adult male rats were divided into: Group I (10 rats) represented control animals, and Group II (30 rats) involved ulcerated rats. The ulcerated group received a single gavage of indomethacin (30mg/kg B.Wt.) and was equally subdivided into: Subgroup ΙΙ-a (ulcerated subgroup), subgroup ΙΙ-b ulcerated rats that received a single intravenous dose of MSCs-MVs (0.5 mg/mL) and subgroup ΙΙ-c ulcerated rats that received ALA (100 mg/kg) orally for 3 days before ulcer induction. Antioxidant enzymes and ulcer index were assessed. Gastric tissue was examined by light and transmission electron microscopes.Results: Indomethacin caused marked damage of the gastric mucosa and ulcer index was significantly higher as compared to the control group. There was loss of the normal histological architecture and inflammatory cells infiltration. Ultrastructure sections revealed increased mucin granules in surface mucous secreting cells. Parietal cells showed dilatation of intracellular canaliculi. In ALA and in MSCs-MVs treated rat groups, there was a significant increase in antioxidant enzyme activities. The structure of the mucosa was significantly improved with a significant decrease in gastric ulcer area. Erosions, necrosis and inflammatory cell infiltration were significantly decreased. No major damage of endothelial cells was observed. The parietal cells count and the VEGF -positive cells were significantly decreased as compared with the control group. Conclusion: MSCs-MVs have significant superior therapeutic effects on gastric mucosa against indomethacin-induced gastric ulcer than the protective effects of α-Lipoic acid (ALA).

Protective effects of α-lipoic acid on cultured human nasal fibroblasts exposed to urban particulate matter.

Exposure to urban particulate matter (UPM) has been studied as a cause of various health problems. Although the association between UPM and the respiratory tract has been well studied, further research is required to characterize the effects of UPM on the upper respiratory tract. We investigated the effects of UPM-induced reactive oxygen species (ROS) production on cultured human nasal fibroblasts, as well as the protective effects of α-lipoic acid (ALA) on ROS production and the underlying signaling pathways involved in ROS inhibition. Human turbinate tissue specimens were collected from 6 patients. The effects of UPM on the viability of cultured nasal fibroblasts were determined. A fluorescent malondialdehyde assay was used to measure ROS levels. Real-time reverse transcription polymerase chain reaction was used to measure the messenger RNA levels of genes encoding Nrf2, the antioxidant response elements (AREs) (HO-1, NQO1), and the proinflammatory cytokines (interleukin-6 and interleukin-8) before and after ALA treatment. Western blotting analyses were used to measure nuclear and cytosolic Nrf2 and AREs. UPM reduced cell viability and increased ROS expression in nasal fibroblasts. ALA treatment decreased ROS production in UPM-exposed fibroblasts via the Nrf2, HO-1, and NQO-1 pathways. Also, ALA treatment abrogated increases in the interleukin-6 and -8 levels induced by UPM in nasal fibroblasts. UPM exposure resulted in increased ROS production in nasal fibroblasts. ALA treatment inhibited this increase via the Nrf2 pathway, suggesting that ALA may have a protective effect against rhinitis caused by ROS expression induced by exposure to UPM.

Protective Effects of α-Lipoic Acid on Hepatic and Renal Biomarkers and Histological Changes Induced by α−Cypermethrin in Treated Male Rats

Protective Effects of α-Lipoic Acid on Hepatic and Renal Biomarkers and Histological Changes Induced by α−Cypermethrin in Treated Male Rats

The protective effect of α-lipoic acid against bisphenol A-induced neurobehavioral toxicity

Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 μM) protected cells from BPA (30 μM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.

Protective Effects of α-lipoic acid on Biological changes Induced by α- cypermethrin in Testis Rats

Abstract a-cypermethrin is one of the most potent insecticides used worldwide. This study was planned to evaluate the possible role of a-lipoic acid in a-cypermethrin induced toxicity in rats. The treated groups were; the control, α-cypermethrin, a-lipoic acid and a-cypermethrin, and a-lipoic acid groups. Our results showed that administration of a-cypermethrin caused a significant decrease in RBC count, PCV, and Hb content and an increase in WBC count. Also, a- cypermethrin caused a significant increase in the levels of cholesterol, TGs, LDL-Cand VLDL-C, while the HDL-C was decreased. Also, a-cypermethrin caused a reduction in serum testosterone, FSH, and LH levels in intoxicated rats. Furthermore, the co-administration of a-lipoic acid mitigated the toxicity of a-cypermethrin by partially normalizing these biochemical parameters. Our results were supported by histopathological observations of the testis. Our data suggest that a-lipoic acid may have a protective role against a-cypermethrin induced toxicity in rats.

α-Lipoic acid inhibits testicular and epididymal oxidative damage and improves fertility efficacy in arsenic-intoxicated rats.

The present study evaluates the protective effect of α-lipoic acid (LA) against arsenic-induced testicular and epididymal oxidative damage in rats. Arsenic caused significant reduction in the reproductive organ weights, serum testosterone levels, testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability, and sperm membrane integrity. Significant reduction in the activity levels of superoxide dismutase, catalase, and glutathione levels with a concomitant increase in the lipid peroxidation and protein carbonyl content in the testis and the cauda epididymis of arsenic-exposed rats. Arsenic intoxication also enhanced the testicular caspase-3 mRNA levels, disorganization of testicular and cauda epididymal architecture as well as increased arsenic content in the testis and the cauda epididymis of rats. Arsenic exposure also deteriorated fertility ability in male rats over controls. Conversely, α-LA negated the testicular and cauda epididymal oxidative stress and restored the male reproductive health in arsenic-exposed rats.

THE AMELIORATING ROLE OF Alpha-LIPOIC ACID SUPPLMENTATION ON ADVERSE EFFECTS INDUCED BY LEAD ACETATE IN BOTH THE HIPPOCAMUS AND THE CEREBRAL CORTEX OF THE MALE ALBINO RATS

The present study focused on two brain areas hippocampus and the cerebral It was designed to investigate the possible mechanisms involved in Lead acetate neurotoxicity and the potential protective effects of α-lipoic acid (α-LA), as an antioxidant against lead-induced neurotoxicity. Fourty adult male albino rats Rattus rattus (each weighing 130 ± 10 g) were divided into four groups (n=8): 1- Normal control group; C: Normal male rats fed ad libitum and allowed a free access of water, and were kept without any treatments. 2- Initiation group (lead-acetate control group; A): Normal male rats received Lead acetate in an interperitoneal dose of 20 mg/kg b.wt daily for two weeks. 3- Treatment group (α-lipoic acid control group; B): Normal male rats were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for three weeks. 4- Pre-initiation treatment group (prophylactic group; D): Normal male rats were intraperitoneally injected with α-Lipoic acid in a dose of 20 mg/kg b.wt daily for one week and then received the above-mentioned dose of the lead acetate for other two successive weeks together with the same dose of α-lipoic acid. 5- Post-initiation treatment group (therapeutic group; E): Normal male rats were intraperitoneally injected once daily with lead acetate (20 mg/kg b.wt) for two weeks then were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for successive three weeks. The levels of lipid peroxidation as malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH), nitric oxide level (NO), and serotonin (5- HT) were estimated in the selected brain regions, the hippocampus and the cerebral cortex, of adult male albino rats in the different groups. These biochemical variables were supported by histopathological examinations by using H&E and toluidine blue staining. Results showed that administration of lead acetate led to enhancement of lipid peroxidation and increased PCC with a concomitant reduction in GSH levels and NO production. In addition, the levels of 5-HT decreased in the hippocampus and the cerebral cortex. However, the administration of α-LA showed a protective effect against Lead acetate-induced neurotoxicity. Rats treated with α-LA showed a corresponding decrease in lipid peroxidation and PCC level. Furthermore, there was an increase in brain GSH level, NO production and level of 5-HT in both brain regions hippocampus and the cerebral Histological studies showed that Lead acetate caused different degrees of neuronal degeneration, focal gliosis, pyknotic neurons, oedema in meninges, cerebral neuropil vacuolization and degenerations. The rats treated with α-lipoic acid revealed an improvement in the histopathological alterations induced by Lead acetate. Finally, the data showed that α-LA has an effect when administered as a therapeutic drug more than as a prophylactic one.

Protective effect of α-lipoic acid against α-cypermethrin-induced changes in rat cerebellum

Alfa cypermethrin is a pyrethroids extensively used as ectoparasiticide in domestic animals, insecticidal spray on cotton, vegetables and other crops and to kill cockroaches, fleas and termites in house and other buildings. Previous studies have shown the adverse effect of α -cypermethrin on brain. This study was planned to evaluate the possible role of α-lipoic acid in α -cypermethrin induced toxicity in brain of male albino rats. Rats were divided into four groups. The control, α-cypermethrin, α-lipoic acid and α -cypermethrin plus α-lipoic acid treated groups. The duration of the experiment was four weeks. Our results showed that the administration of α-cypermethrin caused a significant decreased in γ- aminobutyric acid level, acetylcholinesterase, catalase, superoxide dismutase activities and increase in lipid peroxidation in cerebellum. Furthermore, the co-administration of α-lipoic acid mitigates the toxicity of α-cypermethrin by partially normalizing the biochemical parameters. The biochemical observations were supported by histopathological examinations. The findings of this investigation suggest that α-lipoic acid may play a protective role against α-cypermethrin induced toxicity in cerebellum of treated rats.