The Results of Preclinical Studies Assessing the Effect of Riamilovir on the Reproductive Function and Postnatal Growth of Offspring in Laboratory Animals

Safety assessment of Piper cernuum Vell. (Piperaceae) leaves extract: Acute, sub-acute toxicity and genotoxicity studies

Background: Local cutaneous change is one of the factors involved in the pathophysiology of skin manifestations in chronic kidney disease (CKD). Objectives: To determine the skin’s biophysical parameters in different CKD stages and the relationship with biochemical and hematological parameter, pruritus severity, and body water content. Methods: A cross sectional study involving stage 1 - 5 CKD patients aged ≥ 50 years was performed. Transepidermal water loss (TEWL), hydration, pH and body water content were measured at eight sites. Results: A total of 83 patients aged 66.8 ± 8.4 years participated. There were no differences in TEWL, hydration, pH, and body water between the CKD stages and pruritus severity. Pruritus did not correlate with biophysical, haematological, and biochemical parameters. Hydration correlated with glomerular filtration rate (r = 0.25, P = 0.02, urea r = -0.28, P = 0.01) and creatinine (r = -0.25, P = s0.02). pH correlated with urea (r = 0.34, P = 0.00), creatinine (r = 0.28, v0.01), and hemoglobin (r = -0.28, P = 0.01). Total body water correlated with TEWL, r = -0.25, P = 0.02, but not hydration or pH. Conclusions: There were no differences in TEWL, hydration, pH, body water, and pruritus between non-dialysis CKD stage 1 - 5. Higher urea and creatinine was associated with lower hydration and pH. Increased total body water was associated with lower TEWL. There was no relationship between pruritus with biophysical, haematological, and biochemical parameters.

Canicross is a sport discipline that connects human and canine athletes in running. Changes in physiological, hematological, and biochemical parameters, and exercise-induced oxidative stress have not been thoroughly characterized in canicross dogs. The aim of our study was the assessment of the health status of trained canicross dogs that were subjected to two acute bouts of exercise with their owners during the training season. Health status was assessed by measuring the rectal temperature, hematological and biochemical parameters, as well as blood oxidative stress parameters (plasma malondialdehyde, lipid peroxidation marker; whole blood glutathione peroxidase and erythrocyte superoxide dismutase1, antioxidant enzymes) before and during a two-day canicross training session and after a 24-h rest period. Seven trained canicross dogs (three females/four males) aged 12–120 months were included in the study. Blood samples were collected before and immediately after the first acute bout of exercise (day 1), after the second acute bout of exercise (day 2), and after 24 h of rest (day 3). Rectal temperature was measured at the same time as blood sample collection. The majority of hematological and biochemical parameters remained within reference ranges at all sampling times. Rectal temperature was significantly higher after training on days 1 and 2 compared to resting temperature on day 3. Hematological parameters did not change significantly; however, there were significant differences in urea, creatinine, creatine kinase, and triglycerides between specific sampling times. Despite significant changes, these biochemical parameters remained within reference ranges. Significant changes in biochemical parameters seem to reflect the dogs' physiological response to each acute bout of exercise, considering all biochemical parameters and rectal temperature returned to pre-exercise values after a 24-h rest period (day 3). No significant differences in oxidative stress parameters were found between any sampling times. Relatively high erythrocyte superoxide dismutase1 activity at all sampling times may indicate that the canicross dogs are adapted to training by an increased expression of antioxidant enzymes. Based on our results, we can conclude that the trained canicross dogs included in our study were healthy, in good physical condition, and fit for the two acute bouts of field exercise.

This study analyzed hematological, biochemical, and electrocardiographic parameters in 436 Beagle dogs (9-84 months old) to establish baseline reference indices by age and sex, and to evaluate the effects of these factors on physiological parameters. Age and sex significantly influence physiological parameters, necessitating comprehensive reference ranges across different age groups and sexes. Blood samples and ECG traces obtained from unanesthetized, nulliparous, and non-pregnant dogs, individually housed in controlled environments, ensured the reflection of actual functional parameters while limiting variability. Significant age-related effects were observed in all hematological parameters except ESR, while sex affected only MCH and RDW. Age-sex interactions significantly influenced several hematological metrics, with the most frequent sex-related differences observed in younger dogs (9-24 and 25-36 months-old age-groups). Biochemical analysis showed significant age effects on glucose, cholesterol, HDL, LDL, AST, ALP, CK, TP, ALB, GLB, CREAT, Phosphorous, electrolytes, GGT and TBL, while sex influenced most parameters except TP, ALB, Urea, Calcium, Phosphorous, Sodium, GGT, and TBL. Electrocardiographic analysis revealed significant age and sex effects on p-wave amplitude and PR interval, respectively, with Fridericia’s formula providing the best correction for QT intervals in comparison to Van de Water’s and Bazett’s formulas. Understanding these variations is essential for accurate clinical assessments, ensuring drug safety, and developing tailored interventions in preclinical research.

The study undertook to evaluate the sub-chronic toxicological profile of the seed of Ricinus communis var. minor (RICOM-1013-J), widely used as anticonceptive agent among Bassa people of Plateau State, Nigeria, on haematological and biochemical parameters in adult rats. Thirty-six (36) adult female rats were divided into four groups of 9 rats each, and allowed to acclimatize for 1 week. Group 1 rats served as control and were administered 0.12 ml/Kg vegetable oil subcutaneously. The other rats housed as groups 2, 3 and 4 were treated with 5, 20 and 30 mg/Kg of the extract of RICOM-1013-J as single dose, respectively. Another set of thirty-six (36) adult female rats, also divided into four groups of 9, were similarly treated. 3 rats from each group and from both sets were anaesthetized with 60 mg/Kg phenobarbitone intraperitoneally, and blood samples obtained from the femoral vein for the determination of haematological and biochemical parameters on days 7, 42 and 56 post-treatment. There was no statistically significant difference in haematological parameters between the experimental and control groups in the study. Similarly, although RICOM-1013-J caused general increase in mean levels of the biochemical parameter in treated rats relative to controls, there was also no statistically significant adverse effect on both liver and renal function tests. The study concludes that RICOM-1013-J may have no adverse effect on both haematological and biochemical parameters in rats, and presents a potentially significant breakthrough in family planning technology.Keywords: Ricinus communis; RICOM-1013-J; antifertility; haematological parameters; biochemical indices; safety

Although plants are the major sources of drug, many plants were found to be very toxic when administered systemically. Ethnobotanical surveys reported how reputable Detarium microcarpum is in treating many diseases African countries. To evaluate the effect of 28-day repeated oral administration of flavonoid-rich fraction of Detarium microcarpum stem bark extract on biochemical parameters in Wistar rats. Wistar rats were divided into four groups of five animals each and administered different doses (250, 500 and 1000 mg/kg) of flavonoid-rich fraction via oral route to group II, III and IV respectively while group I received normal saline Body and relative organ weight, liver biomarkers, biochemical (liver and kidney function) parameters, , electrolytes (K, Na, HCO, Cl), and oxidative stress (SOD, MDA, GSH etc.)markers were measured. No significant (P>0.05) increase in body and relative organ weight, liver and kidney function biomarkers (except in BUN at the dose of 1000 mg/kg), oxidative stress markers, electrolytes level and hematological (WBC, RBC, Platelets etc.) parameters in the alkaloid-rich fraction treated rats compared to the normal saline treated group. The flavonoid-rich fraction of Detarium microcarpum stem bark produces no alteration on biochemical and hematological parameters except on oxidative stress markers at higher doses in Wistar rats which, indicated its relative safety.

This study was designed to evaluate the effect of radiation therapy on the oxidative stress, biochemical and hematological parameters in women with breast cancer. 95 women were studied, 20 healthy control women and 75 had breast cancer.Malondialdehyde and glutathione (in erythrocytes and plasma), biochemical parameters (total plasma proteins, plasma albumin, uric acid and plasma calcium) levels, and hematological parameters (hemoglobin, white blood cell counts, platelets counts) all parameters were measured pre- and post radiation therapy for 4 weeks.The result of this study indicates that the incorporation of radiation therapy as a way to destroy malignant cells, in addition to their therapeutic benefits, it may lead to further increase in the oxidative stress burden of cancer, manifested by increase in MDA production and glutathione depletion. Which may affect directly or indirectly some biochemical and hematological parameters as indicated by lowering plasma protein especially albumin, increases in plasma calcium level, and decreases in hemoglobin, white blood cells, and platelets levels.These changes should be considered during radiation therapy and before administration of anticancer drugs or any other drugs because it may affect both the beneficial as well as the toxicity of these drugs.

The aim of this study was to determine some hematological and biochemical parameters in male and female Boer
\nx hair goat crossbreed (n=34). Blood samples were collected from the jugular vein in sample tubes with and
\nwithout anticoagulants. A Mindray BC2800 fully-automated device was used to measure the WBC, RBC, Hgb,
\nHct, MCV, and MCH values and ADVIA 1800 brand auto-analyzer was used to obtain Na, K, Cl, Mg, Ca, Crea,
\nTp, Alb, Gluo, Chol, Trig, AST, ALT, and ALP values. WBC (p<0.01), RBC (p<0.05), HCT (p<0.01) and MCV
\n(p<0.05) levels were found to be statistically higher in female specimens, while HGB and MCH levels were found
\nto be statistically identical for both sexes. Meanwhile, males had statistically higher levels of K (p <0.001) and Mg
\n(p<0.01) levels compared to females. Crea (p<0.001), Tp (p <0.05), Alb (p<0.05), Gluo (p<0.001) levels were
\nalso statistically higher in males, while Chol level was statistically higher in females (p<0.001). No statistically
\nsignificant variation was detected between the Trig values of the sexes. ALT, ALP activities of males were found
\nto be statistically higher in males than in females (p<0.05). The results of the study revealed that some
\nhematological and biochemical parameters of Boer x hair goat crossbreeds are affected by sex.

Introduction: Nanotechnology, a rapidly evolving field, has introduced silver nanoparticles (AgNPs) as promising materials with diverse applications. Their unique properties have revolutionized industries, raising concerns about potential health implications. This study aims to comprehensively evaluate the toxicological effects of AgNPs on rat health through a multidimensional approach, encompassing physiological, hematological, biochemical, and behavioral assessments. Methodology: Colloidal AgNPs with a minimum purity of 99.98% were synthesized using an inductive coupled plasma (ICP) method. Sixty male specific-pathogen-free (SPF) Wistar rats were exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs, alongside a control group. Throughout the exposure period, comprehensive assessments, including body weight changes, food intake, water consumption, hematological and biochemical parameters, and behavioral evaluations, were systematically conducted. The statistical analysis employed a combination of one-way ANOVA and Kruskal-Wallis tests for robust data interpretation. Results: Rats exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs displayed no significant changes in food intake, water consumption, or blood parameters compared to the control group. However, a notable reduction in body weight was observed in the high-dose group, suggesting a potential dose-dependent impact. Biochemical analyses indicated no significant differences in liver and kidney function parameters for the low-dose group, but the high-dose group exhibited potential elevation in liver enzymes, necessitating further scrutiny. Behavioral assessments revealed no significant alterations in open-field behavior or cognitive function, indicating minimal impact on exploratory and cognitive abilities within the tested doses. Conclusion: AgNPs demonstrated minimal impact on certain parameters, the high-dose group exhibited notable body weight reduction and potential liver enzyme alterations, warranting further investigation. Behavioral assessments indicated no significant cognitive effects. These findings emphasize the importance of continued research for informed regulatory decisions and the safe utilization of AgNPs in consumer products.

The objective was to compare the effect of five mineral water mostly consumed in Cameroun on performance, haematological and behavioural parameters in rats. Twenty-four rats (140 g) were used for this study. Among the groups, there are a control group which received deionized water and five experimental groups which received different mineral water (Tangui, Supermont, Opur, Aquabelle and Semme) during 21 days. Rats were allowed for swimming exercise every alternate day between 11h and 17h. On the day 21, rats from each group were subjected to the forced swimming test with tail load. One hour after the forced swimming test, the open field test was carried out to evaluate their behaviour. Water and food consumption, body weight, relative organ weight and haematological parameters were evaluated. Results showed that all the mineral water used during this experimentation did not have any effect on water intake, food consumption, body weight and relative organ weight (p > .05). Significant increase (p < .01 – p < .001) in swimming time of rats consuming Tangui (445.00 ± 43.60 seconds) and Opur (450.80 ± 51.03 seconds) were observed as compared to the control group (325.50 ± 24.37 seconds). Results of behavioural and haematological parameters showed significant modifications in the same groups in comparison with control group (p < .01 – p < .001). Differences of swimming time, hematologic and behavioural parameters observed in rats having consumed Tangui and Opur could be due to the quantity of some minerals (calcium and magnesium) present in those drinks.

Imidacloprid (IMI) is a widely used neonicotinoid insecticide that presents potential risks to non-target avian species. This study investigated the sublethal effects of IMI on the health of the eared dove (Zenaida auriculata), a common granivorous bird in South America. The objective was to characterize the impacts of subchronic oral exposure to IMI on behavioral, physiological, hematological, and biochemical parameters. Eighteen adult male doves (n = 18) were randomly assigned to three groups: a control group receiving water orally, and two treatment groups receiving IMI dissolved in water at doses equivalent to 1/15th (low dose, LD, 3.93 mg/kg b.m.) and 1/5th (high dose, HD, 11.8 mg/kg b.m.) of the oral LD50, administered daily by gavage for 21 days. Health biomarkers measured included water intake, body mass, somatic indices, hematological profiles, and plasma biochemical parameters. Results indicated a significant decrease in body mass in the HD group of doves exposed to IMI. In this group, only an increase in the heterophil/lymphocyte ratio was observed among the hematological parameters. Biochemical parameters showed decreased lactate dehydrogenase (LDH) and increased serum butyrylcholinesterase (BuChE) activities. These findings suggest that IMI, even at sublethal doses, can trigger physiological stress responses, generate metabolic alterations, and exert neurotoxic effects in eared doves. Exposure levels in this study were below those allowed for IMI-treated seeds in Argentina, underscoring the environmental risks to wild birds. Application of sensitive health biomarkers underscores the need for further ecotoxicological research and regulatory measures to mitigate the environmental impact of neonicotinoids on birds.

Changes in some hematological and biochemical parameters during prepartum and postpartum periods in female Baladi goats

The possible consequences of the long intermittent fasting schedule during Ramadan (one month of food and water intake limited to night hours, a practice that is followed by the majority of the Muslims worldwide) on certain biochemical constituents or coagulation variables have not been extensively documented. During the month of Ramadan and two months after, we monitored the concentration of different plasma lipoproteins, lipoprotein (a) [Lp(a)], apoproteins A(1) and B, fibrinogen, factor VII activity and some selected hematological factors in 50 healthy subjects who were employees of institutes related to the Isfahan University of Medical Sciences and aged between 30 and 45 years. The effect of fasting in Ramadan on the relationship between biochemical and coagulation variables was also investigated. The values of apoprotein B, Lp(a) and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio were significantly decreased during Ramadan (P<0.05), while total cholesterol (Tot-C), triglycerides (TG), LDL-C, HDL-C and fasting blood glucose did not change during that month. Among coagulation and hematological factors, fibrinogen level and factor VII activity were significantly decreased during the month (P<0.05). Results also indicated a significant positive association between fibrinogen level and Lp(a), factor VII activity and Tot-C, LDL-C, TG and Apo B during Ramadan. Our findings contribute to a better understanding of previous reports, as the metabolic and coagulation changes that are considered as atherosclerosis risk factors are counterbalanced during Ramadan.

Ficus stuhlmannii Warb. is a medicinal plant used in Africa to treat sickle cell anaemia and various other conditions. The aim of this study was to evaluate the acute toxicity of the methanolic extract of Ficus stuhlmannii Warb. leaves in mice, to contribute to the safety of human consumers. The methanolic extract was obtained after extraction with solvents of increasing polarity and then administered to mice. Its effects on the behaviour, general condition and mortality of the mice were observed. Biochemical and hematological parameters were measured by spectrophotometry. No signs of toxicity were noted after administration of 5000 mg/kg body weight of the methanolic extract of Ficus stuhlmannii Warb. leaves. All animals survived after 14 days of observation, indicating that the LD50 is greater than 5000 mg/kg body weight. Variation in biochemical and haematological parameters is an indicator of acute toxicity. There were no significant differences (p&gt;0.05) in the biochemical parameters between the negative control and the treated groups: dose at 1000 to 500mg/kg, all values found for these parameters were within the normal range. Thus, no significant difference (p&gt;0.05) was observed in the haematological parameters except for white blood cells, where there was a significant difference (p &lt;0.0001) between the control and the groups treated with doses of 2000 to 5000 mg/kg. The results obtained show that the methanolic extract of Ficus stuhlmannii Warb. leaves are not toxic to treated mice, even at a concentration of 5000 mg/kg.

This study reported a preclinical acuteand sub-acute safety profiles of Hermed plus (HP) were investigated in laboratory animals. This is a very effective formulation developed in house. We have systematically studied the effec&nbsp; in Laboratory Animals&nbsp; for its behavioral changes or mortality if any, hematological&nbsp; parameters and found&nbsp; no hepato or&nbsp; renal toxicity associated with the sub-chronic dermal&nbsp; exposure of&nbsp; investigational product&nbsp; in&nbsp; the&nbsp; animals. The study was conducted in female Swiss albino mice using OECD guidelines Number 423. HP was derived from Crataeva nurvala Buch - Ham (Varun) bark, Musa paradisiaca Linn (Kadali / Banana) stem and roots, Achyranthes aspera Linn (Aghada) whole plant and Hordeum vulgare Linn (Yav) seeds. Above materials were converted into Varun bhavi, kadali bhavit, kshars of Kadali, Aghada and Yav respectively and were mixed in certain proportions in GMP certified manufacturing facility to formulate HP capsules form.Acute and sub-acute safety profiles of HP was studied by OECD guidelines Number 423 and FDA guidelines in Swiss albino mice and Wistar rats respectively. For the acute study, HP was administered orally in a single dose of 2000mg/kg and for sub-acute study HP was &nbsp;&nbsp;administered &nbsp;orally using S90,180 and 450mg/kg doses for 90days. In the present sub-acute study at termination the weights of vital organs like adrenals, heart, kidneys, liver, spleen, lungs, testis/ ovaries were determined and were converted into relative % organ weight and these were compared with control rats.In comparison to control animals, the subacute oral therapy with 90 mg/kg, 180 mg/kg, and 450 mg/kg of HP for 90 days to several groups of rats revealed no mortality, no behavioural alterations, and no changes in blood profile, biochemistry parameters, or profiles of essential organs. Hence, the NOAEL for HP in male and female Wistar rats was determined to be &gt; 450 mg/kg when administered orally for 90 days.