scholarly journals Non-clinical safety profile and pharmacodynamics of two formulations of the anti-sepsis drug candidate Rejuveinix

2021 ◽  
Author(s):  
Fatih M. Uckun ◽  
Cemal Orhan ◽  
Joy Powell ◽  
Emre Sahin ◽  
Ibrahim H. Ozercan ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Safety Profile ◽  
Day Treatment ◽  
Recovery Period ◽  
Drug Candidate ◽  
Albino Rats ◽  
Sod Activity ◽  
Clinical Safety ◽  
Significant Difference ◽  
Dose Levels

AbstractHere, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX) have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P or RJX-B similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p <0.0001). There was no statistically significant difference between tissues SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p >0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels.

scholarly journals Non-clinical safety profile and pharmacodynamics of two formulations of the anti-sepsis drug candidate Rejuveinix (RJX)

2021 ◽  
Vol 141 ◽  
pp. 111823
Author(s):  
Fatih M. Uckun ◽  
Cemal Orhan ◽  
Joy Powell ◽  
Emre Sahin ◽  
Ibrahim H. Ozercan ◽  
...  
Keyword(s):  
Safety Profile ◽  
Drug Candidate ◽  
Clinical Safety

Protective effects of erdosteine on rotenone-induced oxidant injury in liver tissue

2004 ◽  
Vol 20 (6-10) ◽  
pp. 141-147 ◽  
Author(s):  
Alpaslan Terzi ◽  
Mustafa Iraz ◽  
Semsettin Sahin ◽  
Atilla Ilhan ◽  
Nuri Idiz ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Tissue ◽  
Antioxidant Properties ◽  
Albino Rats ◽  
Protective Agent ◽  
Protective Effects ◽  
Oxidant Injury ◽  
Sod Activity ◽  
Significant Difference ◽  
Wistar Albino Rats

Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria. This study was undertaken to determine whether rotenone-induced liver oxidant injury is prevented by erdosteine, a mucolytic agent showing antioxidant properties. There were four groups of Male Wistar Albino rats: group one was untreated as control; the other groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5 mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine, respectively. Rotenone treatment without erdosteine increased xanthine oxidase (XO) enzyme activity and also increased lipid peroxidation in liver tissue P < 0.05). The rats treated with rotenone plus erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group PB / 0.05). Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group PB / 0.05). There was no significant difference in nitric oxide (NO) level between groups. There were negative correlations between CAT activity and malondialdehyde (MDA) level (r= -0.934, P <0.05) with between CAT and SOD activities (r= -0.714, P <0.05), and a positive correlation between SOD activity and MDA level (r= 0.828, P <0.05) in rotenone group. In the rotenone plus erdosteine group, there was a negative correlation between XO activity and NO level in liver tissue (r= -0.833, P -0.05). In the light of these findings, erdosteine may be a protective agent for rotenone-induced liver oxidative injury in rats.

scholarly journals HEALING POTENTIAL OF A POLYHERBAL OINTMENT ON EXCISION WOUND IN NORMAL AND DIABETES INDUCED ALBINO RATS

2017 ◽  
Vol 10 (4) ◽  
pp. 41
Author(s):  
Jothi Gnanasekaran ◽  
Keerthana K ◽  
Shobana G ◽  
Radhika J ◽  
Kadhiravan M
Keyword(s):  
Wound Healing ◽  
Ascorbic Acid ◽  
Serum Protein ◽  
Wound Contraction ◽  
Albino Rats ◽  
Equal Proportion ◽  
Sod Activity ◽  
Tissue Protein ◽  
Excision Wound ◽  
Group I

Objective: Wound healing potential of polyherbal ointment prepared from Cordial oblique Willd., Dentophote falcate (L.f) Ettingsh., and Vigna radiate Linn. has been evaluated, Preclinical studies were carried out using albino rats as experiment models.Methods: Animals were divided into 6 groups, each groups comprising of 6 rats. Group I, II and III are normal excision wounded rats that were categorized as normal untreated, polyherbal ointment treated and standard ointment treated respectively. Groups IV, V and VI were induced with diabetes using alloxan monohydrate (150mg/kg bw; ip single dose) and grouped into diabetic untreated, polyherbal ointment treated and standard ointment treated respectively. The polyherbal ointment was prepared by using aqueous extracts of plants in equal proportion with simple ointment base (15% w/w). The Physical, Biochemical and enzymatic parameters studied were rate of wound contraction, ascorbic acid, hydroxyproline, hexosamine, SOD, LPO, serum protein, granulation tissue protein, serum glucose, DNA, RNA, platelet and WBC.Results: The excision wounded animals treated with polyherbal ointment showed a higher rate of contraction and epithelialization during the treatment period. Group II showed 100% and group V showed 90% wound contraction at the end of experimental period. Hydroxyproline, hexosamine, ascorbic acid, tissue protein, DNA, RNA levels and SOD activity were increased significantly (p<0.05), LPO, platelet and serum protein level were decreased with polyherbal ointment treated groups compared to control and standard groups.Conclution: The present study substantiates the traditional claims of plants prepared as polyherbal ointment possessing significant wound healing promoting activity and provides scientific evidence to the ethno medicinal property of plants in healing wounds.Keywords: Wound healing, Polyherbal ointment, Hydroxyproline, Hexosamine, Excision wound, Cordia obliqua Willd., Dentophote falcate (L.f)Ettingsh., Vigna radiata Linn.

Bronchodilating Activity of Formulated Syrup of Jackfruit (Artocarpus heterophyllus Moraceae) Root Extract in Albino Rats

10.17158/335 ◽  
2014 ◽  
Vol 18 (2) ◽  
Author(s):  
Kathleen G. Bersabal ◽  
Angeli B. Alaza ◽  
Charlotte Grace D. De Claro ◽  
Bianca Karla P. Licatan
Keyword(s):  
Leukocyte Count ◽  
Total Leukocyte Count ◽  
Albino Rats ◽  
Root Extract ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Artocarpus Heterophyllus ◽  
Significant Difference ◽  
Histopathologic Evaluation ◽  
Dose Levels

<p>Jackfruit (Artocarpus heterophyllus) root extract, with a bronchodilating agent, is traditionally used for treating asthma. To provide a scientific basis for such claim, this study was conducted to evaluate the safety and efficacy of the formulated syrup of such extract by determining its acute oral toxicity level, approximate effective dose, the significant difference in the total leukocyte count (TLC), total eosinophil count (TEC) and histopathologic evaluation of lung tissue. Female Swiss mice were used to determine the toxicity at selected fixed dose levels of 5, 50, 300 and 2000 mg/kg. Approximate Effective Dose (AED) determination was conducted using female albino rats with a logarithmic increase by 0.6 intervals. Animals were administered with alumovalbumin and desired dose of root extract, respectively. Blood samples were collected for leukocyte and eosinophil counts. It was found that acute oral toxicity was at 2000mg/kg and 5000 mg/kg. AED has significant influence on TLC and TEC at dose levels of 15.85, 251.19, 1000 and 3981.07 mg/ kg. Analysis of Variance showed a significant difference in the mean of the decrease in the total leukocyte count due to the formulated syrup of root extract, Salbutamol (positive control) and plain syrup (negative control). Tukey’s multiple comparison tests, t-test and histopathologic evaluation on the group treated with Salbutamol and root extract formulation showed no significant difference on the TLC and TEC. Salbutamol was not significantly different from the formulated syrup. Hence, both treatments were effective as bronchodilating agents.</p>

scholarly journals Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Dogan Atilgan ◽  
Bekir S. Parlaktas ◽  
Nihat Uluocak ◽  
Fikret Erdemir ◽  
Sahin Kilic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Weight Loss ◽  
Oxidative Damage ◽  
Serum Levels ◽  
Testicular Tissue ◽  
Protein Carbonyl ◽  
Control Group ◽  
Albino Rats ◽  
Sod Activity ◽  
Significant Difference

Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes.Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1), obesity group (Group 2), obesity + MLT group (Group 3), and weight loss group (Group 4). Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system.Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05). Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05). There was no significant difference between groups in terms of mean Johnsen score (P=0.727).Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

1960 ◽  
Vol XXXV (III) ◽  
pp. 381-396 ◽  
Author(s):  
Sven Almqvist
Keyword(s):  
Human Serum ◽  
Normal Serum ◽  
Treatment Level ◽  
Response Curves ◽  
Normal Children ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Humans ◽  
Pre Treatment ◽  
Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

scholarly journals The Effects of Round Window Membrane Injury and the Use of a Model Electrode Application on Hearing in Rats

2021 ◽  
pp. 014556132199018
Author(s):  
Murat Koc ◽  
Abdullah Dalgic ◽  
Mehmet Ziya Ozuer
Keyword(s):  
Hearing Loss ◽  
Cochlear Implant ◽  
Round Window ◽  
Mechanical Trauma ◽  
Round Window Membrane ◽  
Albino Rats ◽  
Topical Steroids ◽  
Distortion Product ◽  
Significant Difference ◽  
Group 3

Objective: To investigate the effects of the mechanical trauma to the round window, a model electrode inserted into the scala tympani on the cochlear reserve, and the efficacy of topical steroids in preventing hearing loss. Materials and Methods: 21 male Wistar Albino rats were equally categorized into three groups. In all groups an initial mechanical injury to round window was created. Only subsequent dexamethasone injection was administrated into the cochlea in the subjects of group 2 while a multichannel cochlear implant guide inserted into the cochlea prior to dexamethasone administration for group 3. Distortion product otoacoustic emissions (DPOAEs) were obtained prior to and immediately after the surgical injury, eventually on postoperative seventh day (d 7). Mean signal/noise ratios (S/Ns) obtained at 2000, 3000, and 4000 Hz were calculated. Data sets were compared with non-parametric statistical tests. Results: The early intraoperative mean S/Ns were significantly less than preoperative measurements for group 1 and 2; however, preoperative and postoperative d 7 average S/Ns did not differ. There was statistically significant difference between preoperative, intraoperative and postoperative d 7 average S/Ns for group 3. Conclusion: We observed that hearing was restored approximately to the preoperative levels following early postoperative repair. However, an electrode insertion into the cochlea via round window subsequent to mechanical trauma seems to cause a progressive hearing loss. Therefore, a special care must be taken to avoid the injury to the round window membrane in the course of the placement of a cochlear implant electrode and surgery for the chronic otitis media.

scholarly journals The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1332
Author(s):  
Gilda M. Iova ◽  
Horia Calniceanu ◽  
Adelina Popa ◽  
Camelia A. Szuhanek ◽  
Olivia Marcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Gingival Tissue ◽  
Control Group ◽  
Albino Rats ◽  
Oxidative Stress Biomarkers ◽  
Significant Difference ◽  
The Impact ◽  
Experimentally Induced

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.

Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Aty Widyawaruyanti ◽  
Arijanto Jonosewojo ◽  
Hilkatul Ilmi ◽  
Lidya Tumewu ◽  
Ario Imandiri ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Healthy Volunteers ◽  
Day Treatment ◽  
Phase 1 ◽  
Andrographis Paniculata ◽  
Control Group ◽  
Healthy Human ◽  
Double Blind ◽  
Random Blood Glucose ◽  
Significant Difference

Abstract Objectives Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers. Methods The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated. Results There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet Conclusions The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic.

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