Paraquat induces different pulmonary biochemical responses in Wistar rats and Swiss mice

The paper presents results showing differential response to paraquat toxicity in Wistar rats and Swiss strain of mice. Paraquat-induced pulmonary biochemical responses in the two animal species were studied at different time point after giving a single intraperitoneal injection of the respective LD(10) doses of the herbicide paraquat to rats and mice. Paraquat induced different biochemical responses including different protective responses in the two animal species. As a protective response, NADPH-specific quinone reductase is induced in rats, while catalase is induced in mice. It is implied that an early induction of catalase in mice as opposed to rats may account for the resistance of Swiss mice to paraquat toxicity. Xanthine oxidase, which was induced in rats, remains unaffected in mice indicating that the enzyme contributes to paraquat toxicity only in Wistar rats. Time-course studies were also conducted to compare the differential responses of antioxidant enzymes and lipid peroxidation between the two species. The results of the study led us to suggest that the manifestation of paraquat toxicity involve distinct differences in early pulmonary biochemical responses in Wistar rats and Swiss mice.     

一种菊科植物抽提物对小鼠血液生化成分的影响

探讨一种菊科植物抽提物对小鼠血液生化成分的影响。利用半自动生化分析仪测定血液生化成分,结果表明该抽提物可降低血清白蛋白和总蛋白含量;降低乳酸脱氢酶、肌酸激酶活性和丙氧酸氧基转移酶活性;对血清中尿素、尿酸、肌酐都有明显降低作用;可减少血清二价金属离子Ca^2 、Mg^2 含量,增加Cl^-含量;对碱性磷酸酶、天冬氨酸氧基转移酶、血清无机磷影响不明显。     

Studies on the acute and sub-chronic toxicity of the essential oil of Ocimum gratissimum L. leaf.

Oral and intra-peritoneal acute toxicity and the sub-chronic intra-peritoneal toxicity of the essential oil of Ocimum gratissimum Linn, Lamiaceae (Ocimum oil), was investigated. The acute toxicity test involved the oral and intra-peritoneal administration of graded doses of Ocimum oil prepared as a 4% v/v emulsion to 2 groups each of 30 rats and mice. LD50 and LD100 were determined for both routes and species. In the sub-chronic toxicity study, 25 male Sprague-Dawley rats were randomized into 4 test groups (treated with three graded sub-lethal doses of Ocimum oil prepared as a 4% v/v emulsion) and a control. Organs and blood samples were taken for analyses after a 30 day treatment period. A dose-dependent sedative effect of Ocimum oil was observed during the acute toxicity study in mice and rats and in the sub-chronic test in rats. Evidence of treatment, route, and dose-dependent toxicity were detected in both studies. Changes in weight of the testes, hearts, kidneys, intestines and lungs of the rats were statistically insignificant (ANOVA P < 0.05). Data analyses of blood biochemical, haematological and histopathological findings showed significant differences between control and treated groups and revealed that Ocimum oil is capable of invoking an inflammatory response that transits from acute to chronic on persistent administration. While the study revealed that Ocimum oil might be better tolerated when administered orally for systemic delivery, the oil has toxic potentialities that should not be overlooked.     

Historical control data from 13-week repeated toxicity studies in Crj:CD (SD) rats

Reference ranges of standard experimental parameters are useful for comparisons in toxicology. The aim of this study was to collect data from 13-week repeated toxicity studies in Crl:CD (SD) rats, a strain widely used for toxicity and efficacy research, for establishing domestic reference values. Data on body weight, food consumption; urinalysis, hematological, and blood biochemical parameters; and organ weights were collected from 11 toxicity studies in 220 Crl:CD (SD) rats (110 males and 110 females). The studies had been performed at a single testing facility over the last 5 years and involved animals sourced from a single breeder. The findings were collated as means, standard deviations, percentages, and ranges. Urine volume, uterus weight, eosinophil, and basophil counts, and triglyceride, total bilirubin, and gamma-glutamyl transpeptidase levels showed standard deviations of 30% or more. These historical control data would help to interpret the effects of test substances in routine toxicity and efficacy studies.     

Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate

BACKGROUND: These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats. METHODS: In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18. Concentrations within the feed were 0, 0.3, 0.6, and 1.0% for the rats and 0, 0.1, 0.3, and 0.7% for the mice. Laparohysterectomies were carried out on the last day of exposure and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The fetuses were weighed, sexed, and examined for external, visceral and skeletal malformations, and developmental variations. The dose rate from dietary DEHT exposure was 0, 226, 458, and 747 mg/kg/day in the rats and 197, 592, and 1382 mg/kg/day in the mice for the control, low, mid, and high-exposure groups, respectively. RESULTS: DEHT exposure did not affect clinical observations. A slight reduction in body weight gain was noted in the high-dose level rat group; the remaining groups were unaffected. At necropsy, increased liver weights were noted in the high-dose rat group and the mid- and high-dose mouse groups. Mean numbers of implantation sites and viable fetuses, mean fetal weights, and mean litter proportions of preimplantation loss, early resorptions, late resorptions, and fetal sex ratios were unaffected by DEHT exposures. No test article-related malformations or variations were observed at any concentration level in the rat and mouse developmental toxicity studies. In the uterotrophic assay for estrogenic activity, sexually immature female rats received oral gavage doses 20, 200, or 2000 mg DEHT/kg bw/day from postnatal day (PND) 19-21. A slight reduction in rate of body weight gain was noted on the first day of dosing in the high dose group, but no other indications of toxicity were evident. DEHT exposure did not affect wet or blotted uterine weight parameters in any of these dose groups. The NOEL for developmental toxicity in rats was 747 mg/kg/day and 1382 mg/kg/day in mice. The NOEL for estrogenic activity was 2000 mg/kg/day. The NOEL for maternal toxicity was 458 mg/kg/day in rats and 197 mg/kg/day in mice. CONCLUSIONS: The lack of adverse developmental effects with DEHT exposure are in contrast to the adverse developmental effects noted after di-2-ethylhexyl phthalate (DEHP) exposure. The difference between the effects noted with the ortho-constituent (DEHP) and the lack of effects reported with the para-constituent (DEHT) is due most likely to differences in metabolism and the formation of the stable monoester, mono-2-ethylhexyl phthalate (MEHP) from the DEHP moiety.     

Acute and chronic toxicity of Nigella sativa fixed oil

We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o. [26.2-31.6] and 2.06 ml/kg body wt. i.p. [1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.     

Maternal toxicity: a possible etiological factor in embryo-fetal deaths and fetal malformations of rodent-rabbit species

Data from animal teratology studies were surveyed to determine whether embryo-fetal mortality and fetal malformations result from a primary action of the agent on the conceptus or if they are secondary to maternal toxicity--a consequence of administration with high dose levels of test chemicals. A fairly strong association between embryo-fetal mortality and maternal toxicity was revealed by analysis of data from hamsters, mice, rats, and rabbits in 234 studies of chemical and physical agents, of which 83 were conducted at both maternotoxic and nonmaternotoxic doses, 94 only at maternotoxic doses, and 49 at nonmaternotoxic doses. In the above studies, only nine chemicals (four each in hamsters and rabbits and one in rats) were reported to induce embryo-fetal deaths at apparently nonmaternotoxic doses. These findings tend to suggest a contributory role for maternal toxicity in the induction of embryo-fetal deaths. The previously reported hypothesis that certain fetal defects in mice may perhaps be caused by maternal toxicity was also found to be true in a review of data on hamsters, rats, and rabbits. Salient maternal toxicity-associated fetal malformations were exencephaly, encephalocele, micro- or anophalmia, and fused ribs in hamsters and defective (fused, missing, or extra) ribs, vertebrae, and sternebrae, ex-, an-, or microphthalmia, and cleft palate in rats and rabbits. These malformations occurred at low frequencies, generally with no readily apparent dose-response relationship. Presumptive evidence indicates that embryo-fetal deaths, and the above-mentioned fetal malformations in experimental animals, which in published literature are presently attributed to chemical induction for a large number of chemicals, may be a consequence of maternal toxicity per se.     

Aqueous Synthesis and Concentration-Dependent Dermal Toxicity of TiO<Subscript>2</Subscript> Nanoparticles in Wistar Rats

A number of dermal toxicological studies using TiO₂ nanoparticles exist which are based on the study of various animal models like mice, rabbits etc. However, a well-defined study is lacking on the dermal toxic effects of TiO₂ nanoparticles on rats, which are the appropriate model for systemic absorption study of nanoparticles. Furthermore, toxicity of TiO₂ nanoparticles varies widely depending upon the size, concentration, crystallinity, synthesis method etc. This study was conducted to synthesize TiO₂ nanoparticles of different sizes (∼15 to ∼30 nm) by aqueous method, thereby evaluating the concentration-dependent toxicological effects of the ∼20-nm sized nanoparticles on Wistar rats. Characterization of the particles was done by transmission electron microscope, dynamic light scattering instrument, X-ray diffractrometer, and ultraviolet spectrophotometer. The toxicity study was conducted for 14 days (acute), and it is observed that TiO₂ nanoparticles (∼20 nm) at a concentration of 42 mg/kg, when applied topically showed toxicity on rat skin at the biochemical level. However, the histopathological studies did not show any observable effects at tissue level. Our data suggest that well-crystallized spherical-shaped ∼20 nm anatase TiO₂ nanoparticles synthesized in aqueous medium can induce concentration-dependent biochemical alteration in rat skin during short-term exposure.     

Age-dependent effects on biochemical variables and toxicity induced by cyclic peptide toxin microcystin-LR in mice

Microcystins are naturally occurring hepatotoxins produced by certain strains of Microcystis aeruginosa and microcystin-LR is the most toxic among the 60 microcystin variants isolated so far. These toxins have been implicated in both human and livestock mortality. In the present study we evaluated the age-dependent hepatotoxic effects of microcystin-LR (MC-LR) in mice after intraperitoneal and oral route of exposure. For acute toxicity studies by intraperitoneal route, 1 LD(50) dose of MC-LR (43.0 microg/kg) was administered to 6- to 36-week-old mice. Results showed that time to death in toxin treated animals decreased with age of mice. In comparison to control mice, treated animals of all age groups showed significant increases in liver body mass index and increases in serum enzymes (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, sorbitol dehydrogenase). For acute oral toxicity studies, 1 LD(50) of microcystin-LR containing extracts (3.5 g of MCE/kg) was administered to 6- and 36-week-old mice. The effects on biochemical variables were similar to intraperitoneal route of exposure. Significant age-dependent effects that were observed in microcystin treated animals by intraperitoneal and oral routes of exposure include: time to death, hepatic lipid peroxidation, glutathione depletion and DNA fragmentation. The age-dependent effects observed in some of the biochemical variables may be due to difference in the amount of microcystin-LR up take and also the age-dependent ability to detoxify the toxin in mice.     

Organ Histopathological Changes and its Function Damage in Mice Following Long-term Exposure to Lanthanides Chloride

Due to increasing applications of lanthanides (Ln) in industry and daily life, numerous studies confirmed that Ln exposure may result in organ damages in mice and rats, while very few studies focused on several organs damages simultaneously. In order to compare the toxicity of Ln on organs, mice were exposed to LaCl(3), CeCl(3), and NdCl(3) of a dose of 20 mg/kg body weight for consecutive 60 days, respectively, then histopathological changes of liver, kidney, and heart, and their function were investigated. The results showed that long-term exposure to Ln caused cell necrosis and basophilia of liver, ambiguity of renal tubule architecture, congestion of blood vessel and capillary of kidney, and heart hemorrhage. The histopathological changes of liver, kidney, and heart in mice caused by Ce(3+) was most severe; the effect by Nd(3+) was slighter than Ce(3+) but more severe than La(3+). The assay of serum biochemical parameters suggested that Ln exposure severely impaired the functions of liver, kidney, and myocardium in mice. These findings suggested that long-term exposure to Ln resulted in histopathological changes of liver, kidney, and heart, and their function damages. Therefore, we thought that long-term application of the products containing Ln on human should be cautious.     

SPF级封闭群SD大鼠血清生化值及凝血酶原时间值的测定

目的建立SPF级（屏障系统）封闭群SD大鼠血液生化及凝血酶原时间正常参考值,为药物长期毒性试验研究者提供参考。方法采用全自动血液生化分析仪检测19周和31周大鼠血液生化值,采用紫外可见分光光度计检测K＋、Na＋、Cl-值和凝血酶原时间值。结果取得19周和31周龄SD大鼠血清生化值和凝血酶原平均值。CR、TG、TC生化指标受年龄及性别因素影响,CR、TG、TC随年龄增长而逐步升高。TBIL、CR、TG、TC、CK、TP、BUN、ALB、AST、K＋、ALP指标雌雄间差异显著（P＆lt;0.05）。结论在药物长期毒性试验中,同一周龄雌、雄SD大鼠K＋、Cl-、Na＋、凝血酶原时间值可合并统计;雌、雄SD大鼠血液生化指标不宜合并统计。在比对正常参考值时应考虑到性别与年龄的因素。     

Effects of certain antitumor platinum compounds on kidney esterases

In a study of the biochemical mechanism of renal toxicity of certain antitumor platinum compounds, particularly cis-dichlorodiammineplatinum(II) (NSC-119875), qualitative and quantitative studies of the soluble nonspecific kidney esterases were carried out using (C57BL/L X DBA/2) mice. There was a major suppression of the testosterone-dependent esterases of treated male mice; these levels dropped to levels below those found in untreated females within 72 h after certain of the drugs were administered. This effect appeared to be in inverse relationship to the numerical value of the LD50 values of the compounds investigated.     

The genetic toxicity of 3,3',4,4'-tetrachloroazobenzene and 3,3',4, 4'-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3',4,4'-Tetrachloroazobenzene (TCAB) and 3,3',4, 4'-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F(1) mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1-30mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50-200mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Vanadium and tungsten derivatives as antidiabetic agents: a review of their toxic effects

Tungstate is an oxyanion that has biological similarities to vanadate. In recent years, a number of studies have shown the antidiabetic effects of oral tungstate in animal models of diabetes. However, because of the tissue accumulation and potential toxicity derived from chronic administration of vanadium and tungsten compounds, the pharmacological use of vanadate or tungstate in the treatment of diabetes is not necessarily exempt from concern. In the context of a potential use in the treatment of human diabetes mellitus, the most relevant toxic effects of vanadium derivatives are reviewed and compared with those reported for tungsten. Hematological and biochemical alterations, loss of body weight, nephrotoxicity, immunotoxicity, reproductive and developmental toxicity, and behavioral toxicity have been reported to occur following exposure to vanadium compounds. Moreover, vanadium also has a mitogenic activity affecting the distribution of chromosomes during mitosis and inducing aneuploidyrelated end points. In contrast to vanadate, studies about the toxic effects of tungstate are very scant. Early investigations in cats, rabbits, dogs, mice, and rats showed that tungstate was less toxic than vanadate when given intravenously. Although in vitro investigations showed a direct effect of tungstate on the embryo and fetus of mice at concentrations similar to those causing effects in vivo, information on the potential cellular toxicity of tungstate is particularly scarce. Taking into account the recent interest of tungstate as a new potential oral antidiabetic agent, an exhaustive evaluation of its toxicity in mammals is clearly necessary.     

Norbixin ingestion did not induce any detectable DNA breakage in liver and kidney but caused a considerable impairment in plasma glucose levels of rats and mice

From the seeds of Bixa orellana are extracted the carotenoids bixin and norbixin that have been widely used for coloring food. In this study, the toxicity of norbixin, purified or not (annatto extract containing 50% norbixin), was investigated in mice and rats after 21 days of ingestion through drinking water. Mice were exposed to doses of 56 and 351 mg/kg (annatto extract) and 0.8, 7.6, 66 and 274 mg/kg (norbixin). Rats were exposed to doses of 0.8, 7.5 and 68 mg/kg (annatto extract) and 0.8, 8.5 and 74 mg/kg (norbixin). In rats, no toxicity was detected by plasma chemistry. In mice, norbixin induced an increase in plasma alanine aminotransferase activity (ALT) while both norbixin and annatto extract induced a decrease in plasma total protein and globulins (P < 0.05). However, no signs of toxicity were detected in liver by histopathological analysis. No enhancement in DNA breakage was detected in liver or kidney from mice treated with annatto pigments, as evaluated by the comet assay. Nevertheless, there was a remarkable effect of norbixin on the glycemia of both rodent species. In rats, norbixin induced hyperglycemia that ranged from 26.9% (8.5 mg/kg norbixin, to 52.6% (74 mg/kg norbixin, P < 0.01) above control levels. In mice, norbixin induced hypoglycemia that ranged from 14.4% (0.8 mg/kg norbixin, P < 0.05) to 21.5% (66 mg/kg norbixin, P < 0.001) below control levels. Rats and mice treated with annatto pigments showed hyperinsulinemia and hypoinsulinemia, respectively indicating that pancreatic beta-cells were functional. More studies should be performed to fully understand of how species-related differences influences the biological fate of norbixin.     

Nefopam enantiomers: preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration

Nefopam (NEF) is a potent analgesic compound administered as a racemic mixture. Previous in vitro and in vivo studies with nefopam enantiomers have shown that (+)nefopam [(+)NEF] is substantially more potent than (-)nefopam [(-)NEF]. Differences between enantiomers have also been suggested in metabolic studies in vitro. The impact of these differences in vivo is not known because there is little or no information on the relative plasma concentrations of the enantiomers or on their kinetics. In this study, individual enantiomers of nefopam were synthesized and examined for acute toxicity in male and female rats and mice. Pharmacologic properties of enantiomers were examined using in vitro binding assays and antinociceptive tests in rats and mice. Additionally, a pharmacokinetic study was conducted in human volunteers. Subjects were administered 20 mg nefopam as Acupan(R) either as a 5- or 20-min intravenous infusion. In a control phase, subjects were administered only vehicle. Blood samples were collected through the following 24 h. Plasma samples were analyzed for individual enantiomers using a chiral assay developed for this purpose. The pharmacologic differences of previous studies were confirmed in receptor binding assays and in the hot plate and the formalin tests in mice. Neither enantiomer demonstrated substantial activity in the tail flick test in rats. No significant differences were revealed between LD(50) values of nefopam enantiomers after oral or intravenous administration in male and female rats or mice. There were no significant differences in AUC(0-infinity), C(max), or half-life between enantiomers following intravenous administration. Based on these findings, there is currently no compelling rationale to justify administering or monitoring individual enantiomers.     

Acute and sub-acute oral toxicity Lagerstroemia speciosa in Sprague-Dawley rats

Through the boost of the natural medicinal market, individuals began to use a variety of organic materials in the marketed herbal preparation. Lagerstroemia speciosa (LS) leaves are known as banaba. People have been using a decoction of LS leaves as antidiabetic. The study aimed to investigate the acute and sub-acute oral toxicity of LS in Sprague-Dawley rats. The acute toxicity was determined by a single oral dose of LS (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The LS (200 mg/kg) was given for 28 days daily in the sub-acute study. The body weight, organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied. The findings of this study showed no mortality or morbidity was found in acute and sub-acute toxicity studies in rats.Additionally, no significant variations were found in the respective weight of organ, haematological and biochemical parameters of treated groups with reference to the control group. Moreover, no visible histological changes were detected in the liver of treated groups with reference to the control. In conclusion, the oral administration of LS did not fabricate any major toxic effect in rats. No toxic consequences were reported during acute and sub-acute toxicity investigations. Overall, LS is a safe, natural bio-actives as studied. Further investigations of cytotoxicity and genotoxicity of the above drug(s) or their combinations may be executed for appreciative safety.     

Is Berlina grandiflora (Leguminosae) toxic in rats?

The toxicity profile of the aqueous methanolic extract of Berlina grandiflora (BG) stem bark was studied in rats. The rats were administered graded doses (125-500 mg/kg p.o) of the extract daily for 21 days and the effects on body weight, organ weight, clinical signs, gross pathology, hematology, histology and serum biochemical parameters were measured. The relative weights of the heart, liver, kidneys and lungs of treated rats were unaffected but there were significant changes in the relative weights of the spleen and testes. The packed cell volume and hemoglobin concentrations were slightly reduced whereas total leucocytes counts were increased remarkably. Alkaline phosphatase and Creatine Kinase levels were reduced in all the groups but Glutamate oxaloacetate was significantly elevated. Total proteins and albumin levels remained normal. BG elicited a significant increase in gamma glutamyl transferase concentrations at 250 mg/kg. No significant changes occurred in urea, uric acid and BUN concentrations but calcium levels shot up remarkably. Histological findings did not reveal any treatment-related effects. The acute toxicity LD50 was estimated to be >2000 mg/kg but dose-related mortality rates of 16.7, 33.4 and 50% were observed during the sub-acute toxicity studies. These findings have once more highlighted the limitations of acute toxicity LD50 testing and suggest that BG may exert varied toxicological effects when administered orally in rats.     

Diclofenac Mediated Demodulation of Alkaline Phosphatase and Renal Cortical Damage in Experimental Albino Mice

Diclofenac sodium is known to interfere with renal physiology by inhibiting prostaglandins. Previous studies indicate that various nephrotoxins damage proximal renal tubules by altering alkaline phosphatase (APase) activity. APase has been reported to be a function related marker in renal proximal tubular epithelia where it is highly expressed. Present investigation deals with toxicity caused in mice kidney at histological and biochemical levels after diclofenac administration. Diclofenac toxicity was assessed by localizing APase in kidney histochemically and biochemically. Intramuscular diclofenac administration (10 mg/kg/body wt) for 30 days exhibited substantial degeneration in kidney. A marked change in APase activity was observed in histochemical and biochemical studies. A change was noticed in specific activity of APase at different periods of diclofenac treatment. Decrease in specific activity of APase after 10 days (18.41 %) and 30 days (55.3 %) of diclofenac exposure was observed. However, an insignificant hike in APase was observed after 20 days of drug therapy. Similar trends in APase activity were evidenced by the electrophoretic analysis. Histological and ultrastructural observations also corroborated above mentioned findings. Present investigation gives an insight into probable mechanism of renal pathology caused by diclofenac administration in mice.     

Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: A novel strategy for the treatment of lead-induced hepato-renal toxicity in rats

Lead (Pb) toxicity affects the hepatic and renal systems resulting to homeostasis imbalance. Curcumin is a strong antioxidant but has restrained clinical applications due to its poor bioavailability. Nanomedicine showed promising potentials in drug delivery and has brought forth the use of cockle shell-derived aragonite calcium carbonate nanoparticles (CSCaCO₃NP) to enhance the effectiveness and targeted delivery of curcumin (Cur). Thus, this study aimed at evaluating the therapeutic effect of curcumin-loaded CSCaCO₃NP (Cur- CSCaCO₃NP) on lead-induced hepato-renal toxicity in rats. Thirty-six male adults Sprague-Dawley rats were randomly assigned into five groups. All groups contained six rats each except for group A, which contained 12 rats. All rats apart from the rats in group A (control) were orally administered a flat dose of 50 mg/kg of lead for four weeks. Six rats from group A and B were euthanized after four weeks of lead induction. Oral administration of curcumin (100 mg/kg) for group C and Cur-CSCaCO₃NP (50 and 100 mg/kg) for groups D and E respectively, commenced immediately after 4 weeks of lead induction which lasted for 4 weeks. All rats were euthanized at the 8th week of the experiment. Further, biochemical, histological and hematological analysis were performed. The findings revealed a biochemical, hematological and histological changes in lead-induced rats. However, treatments with the Cur-CSCaCO₃NP and free curcumin reversed the aforementioned changes. Although, Cur-CSCaCO₃NP presented better therapeutic effects on lead-induced toxicity in rats when compared to free curcumin as there was significant improvements in hematological, biochemical and histological changes which is parallel with attenuation of oxidative stress. The findings of the current study hold great prospects for Cur-CSCaCO₃NP as a novel approach for effective oral treatment of lead-induced hepato-renal impairments.