The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity

Usually, all newborns demonstrate high serum unconjugated bilirubin (UCB) level. UCB may induce adverse effects in the central nervous system. We aimed to evaluate the cytotoxic effects of UCB and the protective effects of docosahexaenoic acid (DHA) on astrocyte cell cultures. The viability of astrocyte cells decreased after UCB treatment in a dose-dependent manner. Pre-incubation of DHA prevents the cells from UCB-mediated neurotoxicity. Our results shown that UCB leads to inhibition of antioxidant enzymes superoxide dismutase (SOD), catalase and GPx activity and induction of apoptosis. But only 4-h pretreatment of DHA can suppress of UCB-mediated inhibition of antioxidant enzymes SOD, catalase and GPx activity and induction of apoptosis in astrocytes. Our results strongly indicated that DHA has a protective effect on UCB-mediated neurotoxicity through inhibition apoptosis and antioxidant enzymes activity of SOD, CAT and GPx in rat primer astrocyte cell line     

Synergistic protective effect of paeoniflorin and β-ecdysterone against rotenone-induced neurotoxicity in PC12 cells

There are several factors, like oxidative stress and neurons loss, involving neurodegenerative diseases such as Parkinson’s disease (PD). The combination of antioxidant and anti-apoptotic agent is becoming a promising approach to fight against PD. This study evaluates the hypothesis that paeoniflorin (PF) and β-ecdysterone (β-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and β-Ecd, hereafter referred to as the PF/β-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and β-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/β-Ecd, but not β-Ecd, inhibited rotenone-triggered protein kinase C-δkinase C-δ (PKCδ) upregulation and nuclear factor κB (NF-κB) activation. β-Ecd or PF/β-Ecd, but not PF, enhanced serine/threonine protein kinase (Akt) activation, promoted nuclear factor E2-related factor 2 (Nrf2) nuclear accumulation, suppressed reactive oxygen species (ROS) production. Neuroprotection of PF/β-Ecd could be completely blocked by PKCδ inhibitor rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKCδ/NF-κB pathway by PF and activation of Akt/Nrf2 pathway by β-Ecd results in a synergistic neuroprotective effect against rotenone-induced neurotoxicity in vitro. These findings provide the rationale for determining the in vivo activity of combined therapy with PF and β-Ecd against PD.     

The protective effect of alpha lipoic acid against traumatic brain injury in rats

Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g–1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na⁺-K⁺ ATPase activities, whereas cytokines (TNF-α, IL-1β) were determined in blood. Brain oedema was evaluated by wet–dry weight method and blood–brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na⁺-K⁺ ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.     

The protective effect of sinapic acid in osteoarthritis: In vitro and in vivo studies

The anti‐inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA‐pretreated human chondrocytes showed lower levels of interleukin (IL)‐1β‐induced IL‐6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor‐α (TNF‐α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase‐9 (MMP‐9) and matrix metalloproteinase‐13 (MMP‐13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‐2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)‐5. Furthermore, activation of nuclear factor κB (NF‐κB), which was induced by IL‐1β, was also inhibited by SA through the pathway of nuclear factor‐erythroid 2‐related factor‐2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.     

Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model

Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10 mg/kg) in the presence/absence of 100 or 250 mg/kg arjunolic acid. Arjunolic acid is given 1 h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects.     

Protective effect of cyclic AMP against cisplatin-induced nephrotoxicity

We reported earlier that reactive oxygen species are implicated in necrotic injury induced by a transient exposure of cultured renal tubular cells to a high concentration of cisplatin but not in apoptosis occurring after continuous exposure to a low concentration of cisplatin. We report here the protective effect of cyclic AMP against cisplatin-induced necrosis in cultured renal tubular cells as well as cisplatin-induced acute renal failure in rats. Several pharmacological agents that stimulate cyclic AMP signaling, including the nonhydrolyzable cyclic AMP analogue dibutyryl cyclic AMP, forskolin, 3-isobutyl-1-methylxanthine, and a prostacyclin analogue, beraprost, prevented cisplatin-induced cell injury in a protein kinase A-dependent manner. Cisplatin enhanced lipid peroxidation, decreased CuZn superoxide dismutase (SOD) while enhancing MnSOD activity, and increased cellular tumor necrosis factor-alpha (TNF-alpha) content. The elevation of TNF-alpha content and cell injury induced by cisplatin were attenuated by p38 mitogen-activated protein kinase (MAPK) inhibitors including SB203580 and PD169316. Indeed, cisplatin increased the number of phosphorylated p38 MAPK-like immunoreactive cells. These intracellular events were all reversed by antioxidants such as N-acetylcysteine (NAC) and glutathione or cyclic AMP analogues. The in vivo acute renal injury after cisplatin injection was associated with the elevation of renal TNF-alpha content. The cisplatin-induced renal injury and the increase in TNF-alpha content were reversed by NAC or beraprost. These findings suggest that cyclic AMP protects renal tubular cells against cisplatin-induced oxidative injury by obliterating reactive oxygen species and subsequent inhibition of TNF-alpha synthesis through blockade of p38 MAPK activation.     

Evaluation of guggulsterone derivatives as novel kidney cell protective agents against cisplatin-induced nephrotoxicity

Guggulsterone derivatives were prepared using [3+2] click chemistry with aryl and alkyl acetylene. The series of derivatives were evaluated for their cellular protective effects on cisplatin-treated cultured LLC-PK1 kidney epithelial cells. Among the guggulsterone-triazole derivatives, compound 6g, which contains a hydroxyl methyl group, was the most active of all the derivatives. In an additional study, we determined that inhibition of the mitogen-activated protein kinase/caspase-3 signaling cascade by 6g mediates its protective effects against cytotoxicity in cultured LLC-PK1 cells.     

Important role of Maillard reaction in the protective effect of heat-processed ginsenoside Re-serine mixture against cisplatin-induced nephrotoxicity in LLC-PK1 cells

The aim of the present study was to verify the important role of Maillard reaction in the protective effect of heat-processed ginsenoside Re-serine mixture against oxidative stress-induced nephrotoxicity. The free radical-scavenging activity of ginsenoside Re-serine mixture was increased by heat-processing. Ginsenoside Re was transformed into less-polar ginsenosides such as Rg(2), Rg(6) and F(4) by heat-processing, and the glucose molecule at carbon-20 was separated. The improved-free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant Maillard reaction products (MRPs) from the reaction of glucose with serine. Moreover, MRPs from ginsenoside Re-serine mixture showed protective effect against cisplatin-induced renal epithelial cell damage.     

The role of salicylic acid in the glutathione-mediated protection against photooxidative stress in rice

Salicylic acid (SA) is known to be an essential component responsible for disease resistance in dicotyledonous plants. In rice, however, tissue contains extremely high endogenous levels of SA that do not increase after pathogen infection, suggesting that the SA has other major functions in healthy leaves. Although involvement of SA in oxidative-stress response is known in some dicotyledonous plants, antioxidative role of SA in rice is obscure. In this study, we examined the involvement of SA in the protection against oxidative stress in rice, using transgenic plants expressing the bacterial nahG gene that encodes salicylate hydroxylase, an SA-degrading enzyme. In SA-deficient NahG rice, the glutathione pool size was constitutively diminished as compared with control plants. NahG seedlings showed a delayed development phenotype, an increased susceptibility to oxidative stress and they developed light-induced lesions in their leaves without pathogen infection. Conversely, treatment with an activator of the SA-mediated defense-signaling pathway, probenazole, increased the glutathione pool size and suppressed lesion formation. These results suggest that in rice, SA has an important role in the response to high-light-induced oxidative stress, through its regulatory effects on glutathione homeostasis.     

The protective effect of ursodeoxycholic acid in alloxan-induced diabetes

The purpose of this work was to study the effect of ursodeoxycholic acid (UDCA) on the morphological and functional alterations in pancreatic islet beta-cells in rats with diabetes induced by alloxan (150 mg kg(-1), i.p.). UDCA (40 mg kg(-1), i.g.) was administered daily from the fifth to the 35th day after the alloxan treatment. The treatment of diabetic rats with UDCA improved the pancreatic morphology disturbed by the alloxan treatment: UDCA increased the number of pancreatic islets and beta-cells, the beta-/alpha-cell ratio and decreased the number of alpha-cells. As the morphometric data suggest, the treatment of diabetic animals with UDCA significantly increased the area of beta-cell cytoplasmatic granules stained by paraldehyde-fuchsin. The concentration of blood glucose in diabetic rats was gradually decreased after the UDCA treatment, and at the end of the experiment reached the control value. The treatment with UDCA raised the serum insulin level in diabetic rats about 2.5-fold, but this concentration was significantly lower as compared to the control group. The content of lipid peroxidation end-products, hydroxyalkenals and malondialdehyde, was significantly elevated in the alloxan-treated rats, whereas the treatment with UDCA normalized these parameters. The present data indicate that UDCA acts as an effective antidiabetic agent in alloxan-induced diabetes and its beneficial effects in diabetic rats can be related to the antioxidant properties of UDCA.     

The protective effect of alpha-crystallin against acute inflammation in mice

Acute inflammation can activate macrophages or monocytes and subsequently release several inflammatory cytokines and reactive oxygen species (ROS). Oxidative stress triggered by the production of ROS plays deleterious role leading to multiple organ failure. This study was designed to investigate the prophylactic effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A and alpha-B subunits in inflammation-induced mice. Mice were divided into three groups (n=6 in each): control, inflammation and alpha-crystallin-treated. Results show that ROS was significantly higher in the lymphocytes, hepatocytes and astrocytes (P<0.05) of inflammation-induced mice when compared to control, but no significant changes were observed in the alpha-crystallin-treated group. Increased level of lipid peroxidation (LPO) and decreased activities of antioxidant such as superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione were observed in the inflammation-induced mice when compared to control, whereas the activities of these were found to be normal followed by alpha-crystallin treatment. We also observed a reduction in reduced glutathione levels in hepatocytes of inflammation-induced mice, which were normalized on alpha-crystallin treatment. The in vitro study has shown that alpha-crystallin treatment not only suppresses the increase in LPO levels but also inhibits the lipid breakdown resulting from autooxidation in mouse cerebral cortex homogenate, and strongly suggests that alpha-crystallin therapy may serve as a potent pharmacological agent in systemic inflammation.     

The effect of salicylic acid on barley response to water deficit

The effect of a moderate (PEG −0.75 MPa) and severe (PEG −1.5 MPa) water deficit on SA content in leaves and roots as well as the effect of pre-treatment with SA on reaction to water stress were evaluated in two barley genotypes — the modern cv. Maresi and a wild form of Hordeum spontaneum. Water deficit increased SA content in roots, whereas SA content in leaves did not change. The level of SA in the roots of control plants was about twofold higher in ‘Maresi’ than in H. spontaneum. After 6 hours of a moderate stress the level of SA increased about twofold in H. spontaneum and about two and a half-fold in ‘Maresi’. Under severe stress conditions the level of SA increased about twofold in the both genotypes, but not before 24 hrs of the stress. Plant treatment with SA before stress reduced a damaging action of water deficit on cell membrane in leaves. A protective effect was more noticeable in H. spontaneum than in ‘Maresi’. SA treatment increased ABA content in the leaves of the studied genotypes. An increase of proline level was observed only in H. spontaneum. The obtained results suggest that ABA and proline can contribute to the development of antistress reactions induced by SA.     

The role of AQP3 and AQP4 channels in cisplatin-induced cardiovascular edema and the protective effect of melatonin

Molecular Biology Reports - The present study evaluates the development of edema, the change in the AQP3, AQP4, p53 and Bax gene expressions, and the protective effects of melatonin in rat hearts...     

The protective effect of newly synthesized compounds against the action of UV-C irradiation on human lymphocytes in vitro

In this work we present our data about the protective effect of the newly synthesized compound 1-(4-fluorphenyltioureido)-4-methyl-piperazyne (FTMP) against high doses UV-C irradiation using human lymphocytes in vitro as a model system. The endpoint used was chromosome aberrations. The genotoxic effect of different UV-C doses in the range from 10 J/m2 to 200 J/m2 was evaluated. Studying the protective effect of FTMP, it was obtained that a low, adaptive concentration (10(-6) mol/l) applied before harmful doses of UV-C irradiation (100 J/M2 and 150 J/M2) induces the yield of chromosome aberrations lower than theoretical, estimated as a sum of single effects of both agents. A tendency for reducing the damage effect of UV-C irradiation was established. The effect is the most clear when a 4-hour interval between the treatments was used. The mitotic index was not affected. These results pointed out the ability of FTMP to decrease the damaging effect of UV-C irradiation in this type of cells and possess the potential to induce the adaptive response against the damaging effect of UV-C irradiation.