Chlorogenic acid co-administration alleviates cisplatin-induced peripheral neuropathy in rats.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is still an unresolved problem in cisplatin (CIS) use. OBJECTIVES: This study investigates possible anti-neuropathic effect of chlorogenic acid (CGA) against CIS-induced CIPN in rats while also investigating the contribution of nitric oxide (NO) to this phenomenon. METHODS: Initially, CGA (250-1000 µM) was tested by MTT assay on primary DRG neurons. Subsequently, CIPN was induced in Sprague-Dawley rats by 3 mg/kg intraperitoneal injections of CIS once/week for 5 weeks. CGA (100 mg/kg) was co-administered with CIS, both alone and in combination with l-arginine (LARG) or l-nitro-arginine-methyl-ester (LNAME), to elucidate the contribution of nitrergic system to anti-neuropathic effects. Mechanical allodynia, thermal hyperalgesia, and cold plate tests were performed to test CIPN. Rotarod, footprint analysis, and activitymeter were used to evaluate motor coordination and performance. Tumor necrosis factor alpha (TNF-α) was measured as a marker of inflammation. Histological evaluations of DRG and sciatic nerves (SNs) were performed utilizing toluidine blue staining. Two-way analysis of variance and Kruskal-Wallis following Tukey's test were used as statistical analysis. RESULTS: Higher concentration of CGA (1000 µM) exhibited protective effect against in vitro neurotoxicity. Neither LARG nor LNAME exerted significant change in this effect. Co-administration of CGA alleviated histological abnormalities and neuropathic effects induced by CIS. Ameliorative effect of CGA was not changed in mechanical allodynia but attenuated in cold allodynia, and motor activity/coordination tests by LARG and LNAME. Neuropathic effects of CIS remained unchanged with LARG and LNAME in behavioral experiments. CONCLUSION: The study identified CGA as candidate agent in mitigating CIPN. NO seems to play a modulatory role in this effect.

The protective effect of taurine on cyclophosphamide-induced testicular toxicity in rats.

This study aimed to evaluate the protective effect of taurine (TAU) with regard to antioxidant, anti inflammatory and antiapoptotic pathways on cyclophosphamide (CP)-induced testicular toxicity in rats. Forty Sprague-Dawley male rats were used in this experimental study. The CP group animals received a single dose of 200mg/kg CP on Day 8 intraperitoneally (i.p). The other groups were treated with TAU (75, 150 and 300mg/kg) orally for 14 days prior to and following a single i.p injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, LH and FSH levels were measured in serum using commercial ELISA kits. The testicular injury induced by CP was evaluated in terms of oxidative stress, inflammation and apoptosis with a significant inflammatory and apoptotic response and an insignificant oxidative stress. TAU treatment resulted in improvement in body weight gain, oxidative stress, inflammation and apoptosis, some of which were significant. The improvement was more pronounced for antiapoptotic effect of taurine in the testis of CP-treated animals. It was concluded that TAU may prevent and/or treat the testicular toxicity by ameloirating oxidative stress, inflammation and apoptosis.

Pro-pre and Postbiotic Fermentation of the Dietetic Dairy Matrix with Prebiotic Sugar Replacers.

In this study, bacterial growth, postbiotic short-chain fatty acids (SCFAs) formation, and gelation properties of sugar-free probiotic milk gels produced with stevia and inulin as a sugar replacer and synbiotic interactions were investigated with regard to prebiotic/bio-therapeutic potential and consumer preference. Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis cultures were used in the manufacture of dietetic milk gels. The addition of stevia and inulin promoted the viability of bacteria and enhanced milk gel firmness throughout its shelf life. The activity of the probiotic bacteria was identified to be within the potential prebiotic effects (> 8.30 log10 cfu mL-1) in a food matrix. However, it was determined that especially stevia and stevia + inulin addition increased the survival rate of probiotic bacteria and in vitro total SCFA production with higher scores for consumers' preferences rather than with the addition of stevia alone. Yoghurts containing B. animalis subsp. lactis have improved the instrumental textural properties, whereas yoghurts containing L. acidophilus had higher scores for sensorial attributes.

In vitro fermentation assay on the bifidogenic effect of steviol glycosides of Stevia rebaudiana plant for the development of dietetic novel products.

The relationship between excessive sugar consumption and many diseases such as dental caries, obesity, diabetes and coronary heart has been increasing in recent years. In this study, utilization of natural sugar replacer steviol glycosides and bifidogenic effect by Bifidobacterium animalis subsp. lactis was assayed in vitro model system. The basal medium (non-carbohydrate containing MRS, Man, Rogosa and Sharpe Agar) were supplemented with 0.025% and 1% stevia, 0.025% stevia + 1% inulin, %1 stevia + 1% inulin. The medium which contained no carbohydrate was designated as negative control, whereas the medium containing 1% glucose or inulin were evaluated as positive and evaluated on the 0, 12, 24, 36 and 48 h of fermentation. Steviol glycosides in both system significantly stimulated the growth of Bifidobacterium animalis subsp. lactis to varying degrees with highest prebiotic activity score, short chain fatty acid production and growth parameters as much as glucose and prebiotic inulin. The viability of the probiotic bacteria was determined within the bio-therapeutic level with potential prebiotic effects depending on the probiotic bacterial strain growing and the type of carbohydrate source utilized. In the study, stevia at lower concentration showed a higher growth rate of with inulin. In conclusion, stevia can be used as functional ingredients for the modulation of the gut microbiota and design of synbiotic systems as a prebiotic substrate and sugar substitute.

Antinociceptive, anxiolytic, and depression-like effects of hydrogen sulfide, nitric oxide, and carbon monoxide in rats and the role of opioidergic and serotonergic systems in antinociceptive activity.

l-Arginine, a nitric oxide (NO) donor; sodium hydrosulfide (NaHS), a hydrogen sulfide (H2 S) donor; and tricarbonyldichlororuthenium(II) dimer (CORM-2), carbon monoxide (CO) donor, are characterized as bioactive gas mediators that have been researched for their roles in human physiology. This study aimed to compare the effects of these mediators on pain, anxiety, and depression. Ninety-one adult male Sprague-Dawley rats were used for the experiments. Locomotor activity, elevated plus maze, forced swimming, tail clip, hot plate, and writhing tests were used for the assessments after the administration of l-arginine (30-100 mg/kg), a NO donor; NaHS (5-10 mg/kg), a H2 S donor; and CORM-2 (5-10 mg/kg), CO donor. Intraperitoneal H2 S, NO, malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels were determined by enzyme-linked immunosorbent assay (ELISA). No statistical significance was found in the locomotor activity. NO and CO significantly extended latency at high doses in tail clip test. No significant activity was observed at any dose of all three substances on a hot plate. Both doses of CO and high doses of NO and H2 S showed an antinociceptive effect in the writhing test. While the opioidergic system plays a role in the spinal antinociceptive effect of l-arginine, both serotonergic and opioidergic systems play a role in its peripheral antinociceptive effect. The serotonergic system plays a role in the peripheral antinociceptive effect of CORM-2. The time spent in open arm increased significantly in all groups an elevated plus maze. High doses of all three substances significantly increased the duration of immobility in the forced swimming test. No statistical significance was observed in MDA, GSH, and TNF-α levels. High doses of NO and CO showed a spinal antinociceptive effect. Both doses of CO and high doses of NO and H2 S showed a peripheral antinociceptive effect. All three agents showed anxiolytic and depression-like effects.

2-Aminoethoxydiphenyl borate ameliorates functional and structural abnormalities in cisplatin-induced peripheral neuropathy.

AIM OF THE STUDY: Cisplatin is a platinum-derived chemotherapeutic agent commonly used in the treatment of various tumors. Ototoxicity, nephrotoxicity, and peripheral neuropathy are the most common side effects of this drug. 2-Aminoethoxydiphenyl borate (2-APB), boron- containing compound, has some protective effects against various tissue damage. The present study aimed to investigate the potential protective effects of 2-APB on in vitro and in vivo cisplatin-induced neurotoxicity. MATERIALS AND METHODS: MTT assay was used to determine cell viability in DRG cells. Peripheral neuropathy was induced in forty male Sprague-Dawley rats (200-250g) by administering cisplatin (3 mg/kg/week) intraperitoneally (i.p) for five weeks. 2-APB (2, 4, and 8 mg/kg, i.p) was administered. Mechanical allodynia, thermal hyperalgesia, cold allodynia, mechanical stimuli, motor coordination, and locomotor activity tests were performed. DRG cells and sciatic nerves were analyzed histologically. NGF, BDNF, TNF-α, GSH, MDA, and LDH levels were investigated in rat DRG tissue homogenates. RESULTS: Our results revealed that 2-APB ameliorated cisplatin-induced neurotoxicity by improving mechanical and cold allodynia and motor coordination impairment. It also reduced cisplatin-induced structural toxicity in peripheral tissues. CONCLUSION: These findings demonstrated that 2-APB could be considered as a potential therapeutic strategy for the treatment of cisplatin-induced peripheral neuropathy.

Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator.

Protein polarization underlies differentiation in metazoans and in bacteria. How symmetric polarization can instate functional asymmetry remains elusive. Here, we show by super-resolution photo-activated localization microscopy and edgetic mutations that the bitopic zinc-finger protein ZitP implements specialized developmental functions - pilus biogenesis and multifactorial swarming motility - while shaping distinct nanoscale (bi)polar architectures in the asymmetric model bacterium Caulobacter crescentus. Polar assemblage and accumulation of ZitP and its effector protein CpaM are orchestrated in time and space by conserved components of the cell cycle circuitry that coordinate polar morphogenesis with cell cycle progression, and also act on the master cell cycle regulator CtrA. Thus, this novel class of potentially widespread multifunctional polarity regulators is deeply embedded in the cell cycle circuitry.