Potential protective effect of honey against paracetamol-induced hepatotoxicity

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase [ALT] and serum aspartate aminotransferase [AST]. Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde [MDA], reduced glutathione [GSH] and glutathione peroxidase [GPx] were also evaluated in the rat liver homogenates. We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta [IL-1beta] because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of II-1beta. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in II-1beta and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage

Taurine: a promising agent of therapeutic potential in experimentally-induced arthritis

Taurine is an amino acid whose protective effects were shown in certain inflammatory conditions. The present work aimed to explore the possible anti-arthritic effects of taurine in comparison with diclofenac. Rats were allocated into five groups [n = 10]. The normal and control groups received normal saline. The remaining three groups were treated with diclofenac [2 mg/kg], taurine [5 mg/kg], or taurine [50 mg/kg], respectively. Drugs were i.p. injected for 26 successive days starting from the onset of adjuvant induction. Arthritis was induced by s.c. injection of 0.4 ml of Freund's complete adjuvant [FCA] into the subplantar region of the right hind paws of rats in all groups except the normal one. Paw volume was measured before and at different time intervals after adjuvant inoculation. After the last measurement, blood samples were collected and were used for estimation of serum levels of lipid peroxides, nitrite, total antioxidants, tumor necrosis factor-alpha, and interleukin-1beta as well as lactate dehydrogenase activity. Histopathological examination of knee tissues of all rats was also performed. Injection of FCA induced marked arthritis manifested by paw edema during the 26-day experiment period. Treatment with diclofenac or taurine [50 mg/kg] markedly inhibited adjuvant arthritis as well as its associated biochemical and histological changes. Taurine [5 mg/kg] did not affect FCA-induced paw edema but it attenuated some of the induced biochemical changes. Taurine effects could be explained by inhibition of pro-inflammatory cytokines production as well as its antioxidant effects

Effects of certain natural products in adjuvant-induced arthritis

The effects of curcumin [80 mg/kg; p.o.] and quercetin [50 mg/kg; p.o.],alone or combined, with diclofenac [2 mg/kg; i.p.] on adjuvant-induced arthritis in rats were studied and compared with diclofenac monotherapy. Experimental arthritis was induced by s.c. injection of 0.4 ml Freund's complete adjuvant [FCA] into the subplanter tissue of the right hind paw of all rats except the normal group [1% tween 80; p.o.]. The test agents were administered daily for 28 days starting from the 1[st] day of adjuvant inoculation. The control arthritic group received the vehicle [1% tween 80; p.o.] daily for the whole experiment period. Assessment of the anti-inflammatory effects of different treatments was done by measurement of paw volume before FCA injection and at different time intervals, for 28 days, thereafter using water plethysmometer. Collection of blood samples was carried out after the last paw measurement [day 28]. They were used for determination of serum lactate dehydrogenase [LDH] activity and levels of serum total antioxidants, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], calcium [Ca[2+]] and nitrite, a stable metabolite of nitric oxide [NO] which reflects its level. In addition, the level of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation was also determined. Histopathological examination of paw tissues was also carried out. Injection of FCA into the hind paw of rats induced marked arthritis manifested by paw edema during the 28-day experiment period. Treatment with diclofenac alone markedly inhibited adjuvant-induced arthritis at all the studied time intervals. Curcumin, alone, reduced FCA induced edema at day 19 only and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at all the studied time intervals. Quercetin, on the other hand, reduced edema during the chronic phase of arthritis at days 19 and 28 and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at day 11 only. FCA resulted in increased levels of serum TBARS, TNF-alpha, IL-1beta and nitrite as well as increased serum LDH activity. Whereas, no significant changes on serum total antioxidants or Ca[2+] levels were noted. Treatments with curcumin or quercetin alone or combined with diclofenac attenuated most of the biochemical changes elicited by FCA. Histopathological examination of paw tissues showed marked vacuolar degeneration and degradation of articular surfaces by FCA injection. Diclofenac and curcumin, alone or combined together, markedly attenuated FCA-induced histopathological changes. On the other hand, quercetin alone or in combination with diclofenac was less protective. In conclusion, the effect of diclofenac monotherapy was still superior compared to curcumin and quercetin. Effects of curcumin and quercetin seem to be mediated through influences on production of pro-inflammatory cytokines, NO level as well as lipid peroxidation

Protective potential of deprenyl in paraquat-induced nephrotoxicity in rats

Deprenyl, a selective and irreversible monoamine oxidase B [MAO-B] inhibitor, has various pharmacological effects unrelated to MAO-B inhibition including antioxidant ones. Paraquat [PQ], a well known herbicide, causes severe nephrotoxicity mediated by redox-cycling and extensive production of superoxide anions in the kidney. The kidney is a primary site for PQ toxicity as it is the main organ of its excretion. Consequently, the possible protective effects of deprenyl [10 mg/kg, i.p.] against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without daily injections of deprenyl for 6 successive weeks. Nephrotoxicity was assessed by measuring serum levels of creatinine, urea nitrogen and uric acid as well as histological examination of kidney sections. Changes in renal oxidant status were monitored by measurements of reduced glutathione [GSH] content and that of thiobarbituric acid reactive substances [TBARS], an index of renal lipid peroxidation. In addition, determination of total nitrate/nitrite [NOx] content, which reflects nitric oxide [NO] content of renal tissues, was performed. Finally, changes in renal enzymatic activities of lactate dehydrogenase [LDH], superoxide dismutase [SOD] and myeloperoxidase [MPO] were also measured. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine and urea nitrogen levels accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS content and increased activities of MPO and SOD. It also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. However, no significant effect was noted on serum uric acid level. Six weeks of regular daily treatment with deprenyl significantly protected against most of PQ-induced biochemical changes evidenced by lowering of elevated creatinine level and reduction of elevated TBARS content and MPO activity. Deprenyl also attenuated PQ-induced depletion of GSH and NOx contents. On the other hand, deprenyl failed to ameliorate PQ-induced effects on serum urea nitrogen level or on kidney cytosolic LDH and SOD activities. Histological examinations of kidney sections revealed marked lesions with PQ especially in renal proximal tubules and fair protection by deprenyl. It could be concluded that deprenyl offered remarkable protection against PQ-induced nephrotoxicity in rats which could expand its use in other areas outside the central nervous system

Neuroprotective effects of deprenyl and certain natural products against paraquat-induced behavioral and neurochemical changes in rats

Paraquat [PQ] belongs to a class of agricultural chemicals known to impact the dopaminergic system adversely causing severe neurotoxicity. PQ was suggested to contribute in the pathogenesis of many neurological disorders including Parkinson's disease. So, the present study aimed to examine the toxic alterations in brain tissue, following sub-chronic treatment with PQ [20 mg/kg, i.p., once weekly for 6 weeks].Three different types of experiments were carried out including behavioral, neurochemical and histopathological ones. Alterations of motor behavioral patterns were examined by testing the locomotor activity using the open field test and the movement coordination using the rotarod apparatus. Changes in brain dopamine [DA] and norepinephrine [NE] contents as well as histopathological examination of brain tissues were accomplished. The possible protective potentials of deprenyl [10 mg/kg; i.p.], quercetin [50 mg/kg; p.o.], green tea extract [1 mg/kg; p.o.] or malt extract [625 mg/kg; p.o.] against sub-chronic PQ-induced neurotoxicity in rats were examined. Results showed that PQ significantly reduced locomotive and motor behaviors. It also provoked remarkable brain damage noted by significant decreases in brain DA as well as NE contents. Furthermore, histopathological examination of PQ-treated brain sections revealed localized focal necrosis and severe loss of neurons. Daily treatment with deprenyl, quercetin and extracts of green tea or malt for 6 weeks significantly ameliorated most of the behavioral, neurochemical and histopathological changes induced by PQ; effects of malt extract being more pronounced. The present results suggest that sub-chronic PQ administration triggers processes characteristic of early stages of dopaminergic neuron degeneration and activates compensatory mechanisms involving both the dopaminergic and noradrenergic transmissions. Considering the present behavioral studies, neurochemical analysis and histopathological observations, one can conclude that the used agents could be of therapeutic potentials in protection against PQ- induced neurotoxicity

Nephrotoxicity induced by long-term administration of paraquat in rats: protective effects of quercetin and extracts of malt and green tea

Paraquat [PQ], a well-known herbicide, causes nephrotoxicity mediate by redox-cycling and extensive production of superoxide anions in the kidney. The possible protective effects of three natural products namely; green tea extract [I mg/kg], malt extract [625 mg/kg] and quercetin [50 mg/kg], against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without oral daily treatment with any of the three agents for 6 consecutive weeks. Nephrotoxicity was assessed by measuring serum creatinine level, histological examination of kidney sections and calculation of percentage kidney-to-body weight of rats. In addition changes in enzymatic activities of superoxide dismutase [SOD], lactate dehydrogenase [LDH] and myeloperoxidase [MPO], as well as reduced glutathione [GSH], protein thiols [Pr-SHs] and total nitrate/nitrite [NOx] contents of renal tissues were determined. Renal lipid peroxidation was also assessed by measurement of the levels of thiobarbituric acid reactive substances [TBARS]. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine level accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS level and increased activities of MPO and SOD. PQ also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. On the other hand, no significant effect was noted on percentage kidney-to-body weight of rats or on renal Pr-SHs contents. Six weeks of regular daily treatment with any of the chosen agents significantly protected against most of PQ-induced biochemical changes. Histological examinations of kidney morphological changes revealed marked lesions with PQ especially in renal proximal tubules and variable degrees of protection by the test agents with the best results produced by malt extract and quercetin and to lesser extent by green tea extract. It could be concluded that malt extract and quercetin offered remarkable protection against PQ-induced nephrotoxicity in rats. Green tea extract produced some beneficial effects on the biochemical events associated with PQ-induced nephrotoxi city