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

Low dose gamma irradiation modifies the effect of L-carnitine, curcumin, garlic powder and green tea extract on doxorubicin-induced nephropathy in rats

The possible protective potential of exposure to low dose of gamma radiation in presence or absence of L-carnitine, curcumin, garlic powder or green tea extract was examined in the present study on doxorubicin [DOX]-induced experimental nephropathy in rats. Preliminary study was carried out to select the suitable dose of DOX to induce nephrotoxicity. In the current experiment 5 mg/kg, i.p. was selected as a single dose to induce nephrotoxicity during 15 days. The possible modulating effect of L-carnitine, curcumin, garlic powder or green tea extract on kidney function was examined. Animals were subdivided into three sets. Three groups of the 1[st] set were exposed to [gamma] radiation at a single dose level of 0.3 Gy then received DOX, 1, 3 or 7 days postirradiation respectively. The groups of 2[nd] set daily received L-carnitine [40 mg/kg, i.p.], curcumin [50 mg/kg, i.p.], garlic powder [100 mg/kg, p.o.] and green tea extract [300 mg/kg, p.o.] daily for two weeks before induction of nephropathy. Groups of the 3[rd] set received the same doses of drugs then were injected with DOX, 1, 3 or 7 days following gamma irradiation respectively. Two groups of animals, one of them received saline and served as normal and the other received DOX and served as nephropathic group were included in 1[st], 2[nd] as well as 3[rd] set. Fifteen days following DOX administration, serum was collected and the animals were then sacrificed. Serum creatinine, urea and uric acid were evaluated. Data revealed that, a single DOX dose [5 mg/kg] induced marked acute nephrotoxicity manifested as significant increase in the activities of serum creatinine, urea as well as uric acid. Interestingly, pre-exposure to gamma radiation at a dose level of 0.3 Gy, 1 or 3 days before DOX injection exhibited significant improvement in the above altered mentioned parameters. However, exposure to low dose radiation 7 days prior to DOX administration did not show a protective effect. Moreover, pretreatment with L-carnitine, curcumin, garlic powder or green tea extract in rats unexposed or exposed to gamma radiation before DOX administration ameliorated, to a great extent, the effects induced by DOX. The present findings suggest that exposure to a single low dose of gamma radiation [0.3 Gy] one day before DOX administration is a promising approach for maximizing the nephroprotective effects of L-carnitine, curcumin, garlic powder or green tea extract with minimal adverse effects of DOX

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

Protective effects of amlodipine, coenzyme Q10 and their combination on myocardial ischemia/reperfusion injury in rats

Ischemia/reperfusion [I/R] injury is of major clinical relevance during ischemic heart diseases, percutaneous transluminal angioplasty, coronary artery bypass and heart transplantation. Amlodipine, a calcium channel blocker, exhibits antioxidant and antiproliferative activities as well as eNOS activation that could help in cardioprotection following I/R insult. Coenzyme Q10 [CoQ], a mitochondrial coenzyme involved in oxidative phosphorylation, possesses strong antioxidant and lipid peroxyl neutralizing functions. The current study demonstrated the possible cardioprotection of amlodipine [15 mg/kg/day] and CoQ [200 mg/kg/day] alone or in combination against myocardial I/R-induced functional, metabolic and cellular changes. Drugs were administered orally for one week. Rats were then subjected to myocardial I/R [35min/10min]. Heart rates and incidence of ventricular arrhythmias were recorded during l/R progress. At the end of reperfusion, blood samples were collected for estimation of plasma creatine kinase [CK] activity. The left ventricle homogenates were used for determination of lactate, ATP, thiobarbituric acid reactive substances [TBARS], reduced glutathione [GSH] and total nitrate/nitrite [NOx] contents as well as myeloperoxidase [MPO] activity. Finally, histological examination was performed to visualize the possible cellular effects of the drugs. Amlodipine, CoQ and their combination significantly protected against reperfusion-induced tachycardia and decreased the incidence and severity of arrhythmias. Amlodipine afforded a significant degree of protection against plasma CK elevation and myocardial GSH depletion, while it completely protected against myocardial MPO, lactate and TBARS elevation. On the other hand, it failed to defend against ATP depletion and NOx elevation. CoQ provided a significant degree of protection against plasma CK, myocardial MPO, NOx elevation and ATP depletion. It completely protected against GSH depletion, lactate and TBARS elevation. Combination therapy provided significant increase in myocardial ATP and GSH contents and significant decrease in plasma CK activity in comparison with amlodipine monotherapy. It could be concluded that adding CoQ to amlodipine therapy offered remarkable improvement in the cardioprotective effect of amlodipine

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

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

Hysteroscopic tubal cannulation under laparoscopic guidance for diagnosis and treatment of proximal tubal obstruction

The narrowest portion of the human fallopian tube extending from the uterotubal ostium to the ampullary-isthmic junction is exceptionally vulnerable to pathogenic organisms and other insults which often induce block of this narrow segment. Proximal tubal obstruction [PTO] exists in about 20% of patients with tubal infertility, and frequently is an isolated finding with otherwise normal pelvic anatomy. PTO presents a significant diagnostic and therapeutic problem. Several reports in the literature suggest that up to two-thirds of fallopian tubes resected for PTO reveal an absence of transluminal or luminal pathology. Conventional HSG or even laparoscopic chromopertubation may not determine whether the visualized obstruction is due to a temporary cause such as cornual spasm and loose mechanical blocks, or whether true anatomic occlusion exists. This differentiation is critical in determining the type of therapy offered to the patient. Only true pathologic tubal occlusion necessitates either IVF or microsurgical tuboplasty. To present the diagnostic findings, the immediate and the remote tubal patency rates, and the reproductive outcome following hysteroscopic tubal cannulation performed under laparoscopic guidance, for the patients with proximally obstructed fallopian tubes. PTO was diagnosed by three approaches HSG, laparoscopic transcervical chromopertubation, and hysteroscopic/laparoscopic transostial selective chromopertubation. Prospective observational clinical study presenting the laparoscopic/hysteroscopic findings in patients with proximal tubal occlusion, and discussing the immediate and the remote tubal patency rates and the reproductive outcome following hysteroscopic tubal cannulation under laparoscopic guidance. Tanta University Hospital and private centers. Thirty-nine consecutive infertile women who had bilateral PTO on HSG and subsequently underwent combined laparoscopy and hysteroscopy were evaluated. Seventeen women were found to have bilateral PTO as an isolated finding with otherwise normal pelvic anatomy and intact other fertility factors. In these 17 women the diagnosis of PTO was based on the initial findings of HSG, supported by the results of laparoscopic transcervical chromopertubation, and finally confirmed by hysteroscopic/laparoscopic transostial selective chromopertubation. In trial to relieve PTO in these 17 women, hysteroscopic tubal cannulation was performed. A coaxial cannulation set composed of a Labotect flexible guide cannula, a 3-French end-hole Teflon ureteric catheter, and a Teflon-coated stainless steel urologic guidewire were utilized for hysteroscopic tubal cannulation under laparoscopic guidance. The immediate on-table success of tubal cannulation evidenced by intraoperative tubal patency rate documented by laparoscopic chromopertubation, the long term persistence of achieved tubal patency evidenced by the remote tubal patency rate documented by HSG performed 6 months after the procedure for those patients who did not conceive, and the reproductive outcome following the hysteroscopic tubal cannulation meaning the pregnancy rate achieved during the follow up period of six months. The average age [ +/- SD] of the patients was 27.3 +/- 3.5 yean [range 22-35 years], and the mean duration of infertility [ +/- SD] was 3.61 +/- 1.2 years [range 2-7 years]. Fourteen women [35.90%] presented with primary infertility and 25 women [64.10%] presented with secondary infertility. Laparoscopic transcervical chromopertubation demonstrated proximall tubal patency in 7 [17.95%] out of the 39 women; and hysteroscopic/ laparoscopic transostial selective chromopertubation demonstrated tubal patenq in another 4 [10.26%] women. This means 28.21% false +ve results for HSG, and 10.26% false +ve results for laparoscopic transcervical chromopertubation. Successful tubal cannulation with achievement of immediate tubal patency was evident in 24 [70.59%] tubes present in 13 [76.47%] patients. Tubal patency was achieved bilaterally in 11 patients, and unilaterally in 2 patients. Initial total failure of the procedure [i.e. inability to achieve tubal patency in either of both tubes whether due to inability of tubal cannulation or due to persistence of PTO after tubal cannulation] was evident in 4 [23.53%] patients. Inability of tubal cannulation was evident in 6 [17.56%] tubes present in 4 patients. Persistence of tubal occlusion after cannulation was observed in 4 tubes [11.76%] present in 3 patients. Tubal perforations have complicated the tubal cannulation of 5 [14.70%] tubes, Three of the perforations were associated with persistence of tubal occlusion, and the other two perforations were associated with successful tubal cannulation and restoration of tubal patency. Six women [35.29%] achieved intrauterine pregnancies, and one patient [5.88%] had a tubal ectopic pregnancy. HSG, performed six months after tubal cannulation for the patients who did not conceive, revealed preservation of tubal patency in 4 [23.53%] patients, and bilateral tubal reocclusion in 2 [11.76%] patients. Hysteroscopic tubal cannulation under laparoscopic guidance has a major impact on the management and counseling of infertile wmen with PTO. IVF is a present first choice for treatment of tubal factor infertility, but IVF is still stressful economically and physically. On the other hand, pregnancies achieved naturally are not only inexpensive but also easy for the patients from all aspects. Hysteroscopic tubal cannulation is a safe and cost effective procedure which has clear diagnostic and therapeutic benefits for infertile patients with PTO. Considering the success rate of hysteroscopic tubal cannulation, about three-fourths of the patients with PTO managed by this technique are recommended to try to conceive naturally, instead of being referred for ART or microsurgery. Hysteroscopic tubal cannulation under laparoscopic guidance should be recommended as first choice for further diagnosis and treatment of infertile women with PTO

Intrauterine insemination with avarian hperstimulation for treatment of comples with unexplained infertility

Treatment of couples with unexplained infertility includes many therapeutic modalities that range from expectant management to the most sophisticated assisted reproductive techniques [ARTs] as IVF and GIFT. As such, we evaluated the clinical efficacy of ovarian hyperstimulation with intrauterine insemination [IUI] as an easy and economic method of ARTs for treatment of couples with unexplained infertility. A total of 112 couples with unexplained infertility, despite of the normal finding of the infertility diagnostic work-up, were selected for this study. The male partner was evaluated by history taking, physical examination, scrotal doppler examination for varicocele, 3 consecutive semen analysis, and hormonal profile that included FSH, LH, prolactin and testosterone. The protocol of female evaluation included history taking, clinical examination, postcoital test, hormonal assay for serum prolactin, luteal phase of serum progesterone and thyroid function test, ultrasound pelvic examination with ovarian folliculometry, hysterosalpingography, premenstrual endometrial biopsy laparoscopy and hysteroscopy. All selected couples were managed by controlled ovarian hyperstimulation in combination with IUI for up to 3 cycles. Vaginal ultrasound scan was used for monitoring of the treatment cycles. A total of 171 treatment cycles were made and 27 clinical pregnancies were achieved [25 term and ongoing pregnancies and 2 spontaneous abortions]. The total pregnancy rate was 24.1% per patient and 15.8% per treatment cycle. The successful pregnancy rate was 22.3% and 14.6% per patient and per treatment cycle respectively. Controlled ovarian hyperstimulation in combination with IUI achieved a reasonable success rate in the treatment of couples with unexplained infertility and should be offered before considering the more sophisticated and expensive assisted reproductive techniques