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Aim: This study aims to explain all the events of skeletal muscle repair and regeneration with the help of suitable histophathlogical photomicrographs taken from crush-injured adult albino rat’s gluteus maximus muscle. Materials and Methods: The present study is part of our previous research study related to skeletal muscle repair and regeneration in crush injured gluteus maximus muscle of adult albino rats. The samples were processed for histopathological examination using routine and special histological staining procedures. The tissue samples were examined under trinocular microscope, and the fields showing interesting findings were recorded under different magnification. Results: In this study we observed all regenerative changes in myofibers and related structures after crushed injury. Conclusion: Histopathological studies with good stainings are helpful for the easy identification of minute changes that occurs in each stages of skeletal muscle regeneration.

Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl2) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Adult male Wistar rats were divided into four groups and separately administered a single oral dose of 5, 15, 30 and 40 mg CuCl2/kg body weight. Rats not administered CuCl2 served as the control. Oral administration of CuCl2 led to significant alterations in the activities of metabolic and membrane-bound enzymes; brush border enzymes were inhibited by 45-75% relative to the control set. Inhibition of antioxidant enzymes diminished the metal-reducing and free radical quenching ability of the cells. Oxidative damage caused cellular oxidation of thiols, proteins and lipids. Diphenylamine and comet assays showed that CuCl2 treatment enhanced DNA damage while DNA-protein crosslinking was also increased in the intestinal cells. Examination of stained sections showed that CuCl2 treatment led to marked histological changes in the intestine. All the changes seen were in a CuCl2 dose-dependent manner with more prominent alterations at higher doses of CuCl2. These results clearly show that oral administration of CuCl2 results in oxidative damage to the intestine which can impair its digestive and absorptive functions.

Pentachlorophenol (PCP) is a broad spectrum biocide that has many domestic and industrial applications. PCP enters the environment due to its wide use, especially as a wood preservative. Human exposure to PCP is through contaminated water and adulterated food products. PCP is highly toxic and is classified as class 2B or probable human carcinogen. In this study, we explored the effect of PCP on rat intestine. Adult rats were orally given different doses of PCP (25–150-mg/kg body weight/day) in corn oil for 5 days, whereas controls were given similar amount of corn oil. The rats were sacrificed 24 h after the last treatment. A marked increase in lipid peroxidation, carbonyl content, and hydrogen peroxide level was seen. The glutathione and sulfhydryl group content was decreased in all PCP treated groups. This strongly suggests the generation of reactive oxygen species (ROS) in the intestine. PCP administration suppressed carbohydrate metabolism, inhibited enzymes of brush border membrane (BBM), and antioxidant defense system. It also led to increase in DNA damage, which was evident from comet assay, DNA-protein cross-linking, and DNA fragmentation. Histological studies supported the biochemical results showing marked dose-dependent tissue damage in intestines from PCP treated animals. This study reports for the first time that oral administration of PCP induces ROS, impairs the antioxidant system, damages DNA, and alters the enzyme activities of BBM and metabolic pathways in rat intestine.

Herein, for the first time, heterojunctions containing nano-hydroxyapatite/carboxymethyl chitosan/β-cyclodextrin fused with date seed extract (DSE) were synthesized at different concentrations using co-precipitation to generate BCHD1, BCHD2 and BCHD3 nanocomposite scaffolds with tunable size and amendable surface properties. FTIR, XRD and mechanical analysis studies confirmed the presence of different constituents in the proposed nanocomposite scaffolds displaying strong interactions with an optimal compressive modulus shown by BCHD3 [1533 ± 2.69 MPa], relative to nano-hydroxyapatite/carboxymethyl chitosan (CH) nanocomposite scaffolds. The results of TEM, water contact angle and SEM revealed the homogenous distribution of needle-shaped particles having an average size ranging between 18 and 25 nm with a moderate hydrophilicity [WCA = 42.5°] and an interconnected rough morphology. Furthermore, the BCHD nanocomposite scaffolds were investigated for their biomimetic mineralization ability using simulated body fluid by mimicking the inorganic composition of human blood plasma, which demonstrated superior hydroxyapatite nucleation. The BCHD3 nanocomposite scaffolds showed an advanced protein adsorption [130 ± 41 μg cm−2] and active alkaline phosphatase performance and did not exacerbate lactate dehydrogenase leakage of MG63 osteoblast-like cells relative to CH. The comprehensive in vivo study identified better bone regeneration in the repair of critical size calvarial defects [8 mm] in albino rats upon treatment with BCHD3, which is selectively tested as a bare implant in comparison to cerabone, as corroborated by the histopathological and radiological investigations with an average GBD of 94.5 ± 1.24%. Therefore, the above-mentioned results have shed more light on establishing the efficiency of BCHD3 to find applications in osteogenic tissue engineering.

Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl

Thiram is a dithiocarbamate pesticide that is widely used as a fungicide to protect crops and seeds, especially in China and India. Although thiram is considered relatively safe for humans but due to its persistent nature it may become a health hazard for human beings and animal if long term exposure takes place. The aim of the present work was to study the effects of oral administration of thiram on kidney of male rats given different doses of thiram (100, 250, 500, 750 mg/kg body weight) for 4 consecutive days. This treatment significantly reduced cellular glutathione and total sulfhydryl content but enhanced protein carbonyl and hydrogen peroxide levels. The plasma creatinine and BUN levels were also elevated indicating nephrotoxicity. The activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, thioredoxin reductase and glutathione-S-transferase were significantly decreased. The antioxidant capacity was diminished resulting in less free radical quenching and metal reducing ability of kidney. Administration of thiram also led to inhibition of intestinal brush border membrane enzymes: alkaline phosphatase, leucine aminopeptidase, γ-glutamyl transferase and maltase. Activities of enzymes of glucose metabolism viz. glycolysis, citric acid cycle, pentose phosphate pathway and gluconeogenesis were also inhibited. Histopathology of kidney tissue revealed tubular dilation, tubular cast, breaking of apical cytoplasm and intestinal hemorrhage. A significant increase in DNA fragmentation, DNA strand breaks and DNA-protein cross-linking was also observed in thiram treated rats compare to control group. These changes in kidney could be due to marked perturbation in antioxidant defense system induced by free radicals generated upon exposure to thiram.

Pesticides are extensively employed worldwide, especially in agriculture to control weeds, insect infestation and diseases. Besides their targets, pesticides can also affect the health of non-target organisms, including humans The present study was conducted to study the effect of oral exposure of thiram, a dithiocarbamate fungicide, on the intestine of rats. Male rats were administered thiram at doses of 100, 250, 500 and 750 mg/kg body weight for 4 days. This treatment reduced cellular glutathione, total sulfhydryl groups but enhanced protein carbonyl content and hydrogen peroxide levels. In addition, the activities of all major antioxidant enzymes (catalase, thioredoxin reductase, glutathione peroxidase and glutathione-S-transferase) except superoxide dismutase were decreased. The antioxidant power of the intestine was impaired lowering the metal-reducing and free radical quenching ability. Administration of thiram also led to inhibition of intestinal brush border membrane enzymes, alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase and sucrase. Activities of enzymes of pentose phosphate pathway, citric acid cycle, glycolysis and gluconeogenesis were also inhibited. Histopathology showed extensive damage in the intestine of thiram-treated rats at higher doses. All the observed effects were in a thiram dose-dependent manner. The results of this study show that thiram causes significant oxidative damage in the rat intestine which is associated with the marked impairment in the antioxidant defense system.

The widespread use of sodium nitrite (NaNO2 ) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO 2 is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO 2 -induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO 2 at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO 2 induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO 2 -treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO 2 -induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.

The widespread use of sodium nitrite (NaNO2) as food preservative, rampant use of nitrogenous fertilizers for agricultural practices, and improper disposal of nitrogenous wastes have drastically increased human exposure to high nitrite levels causing various health disorders and death. In the present study, the protective effect of carnosine and N-acetylcysteine (NAC) against NaNO2-induced intestinal toxicity in rats was investigated. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either carnosine at 100 mg/kg body weight/day for 7 days or NAC at 100 mg/kg body weight/day for 5 days. Rats were killed after 24 h, and intestinal preparations were used for the evaluation of biochemical alterations and histological abrasions. Administration of NaNO2 alone decreased the activities of intestinal brush border membrane and metabolic enzymes and significantly weakened the anti-oxidant defense system. DNA damage was also evident as observed by increased DNA-protein crosslinking and fragmentation. However, prior administration of carnosine or NAC significantly ameliorated NaNO2-induced damage in intestinal cells. Histological studies support these biochemical results, showing intestinal damage in NaNO2-treated animals and reduced tissue injury in the combination groups. The intrinsic anti-oxidant properties of carnosine and NAC must have contributed to the observed mitigation of nitrite-induced metabolic alterations and oxidative damage. Based on further validation from clinical trials, carnosine and NAC can potentially be used as chemo-preventive agents against NaNO2 toxicity.

Sodium nitrite (NaNO2 ) is widely used as a food additive and preservative in fish and meat products. We have evaluated the effect of a single acute oral dose of NaNO2 on oxidative stress parameters, antioxidant capacity, and DNA in rat kidney. Male Wistar rats were divided into four groups and given single oral dose of NaNO2 at 20, 40, 60, and 75 mg/kg body weight; untreated rats served as the control group. All animals in NaNO2 -treated groups showed marked alterations in various parameters of oxidative stress as compared to the control group. This included increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels, and decrease in reduced glutathione content and antioxidant capacity. Administration of NaNO2 also increased DNA damage as evident from release of free nucleotides and confirmed by comet assay. It also led to greater cross-linking of DNA to proteins. Histological analysis showed marked morphological changes in the kidney of NaNO2 -treated animals. These alterations could be due to increased free radical generation or direct chemical modification by reaction intermediates. Our results suggest that nitrite-induced nephrotoxicity is mediated through redox imbalance and results in DNA damage.

We have previously shown that oral administration of Nigella sativa oil (NSO) ameliorates the deleterious gastrointestinal effects of cisplatin (CP), administered as a single dose. Since a typical clinical CP dosing regimen involves multiple cycles of CP administration in lower doses, in the present study we investigate the protective efficacy of NSO and its major bioactive constituent, thymoquinone (TQ), against multiple-dose CP treatment-induced deleterious biochemical and histological changes in rat intestine. Rats were divided into six groups, viz., control, CP, CP+NSO, CP+TQ, NSO, and TQ. Animals in CP+NSO and CP+TQ groups were pre-administered NSO (2 ml/kg bwt, orally) and TQ (1.5 mg/kg bwt, orally), respectively, daily for 14 days and were then treated with five repeated doses of CP (3 mg/kg bwt, i.p.), every fourth day for 20 days while still receiving NSO/TQ. CP treatment alone led to a significant decline in specific activities of brush border membrane (BBM) enzymes while NSO or TQ administration to CP-treated rats significantly prevented the decline in BBM enzyme activities in the isolated brush border membrane vesicles (BBMV) as well as in mucosal homogenates. Furthermore, both NSO and TQ administration markedly ameliorated CP-induced alterations on carbohydrate metabolism enzymes and the enzymatic and non-enzymatic parameters of antioxidant defense system in the intestinal mucosa. However, NSO appeared to be more efficacious than TQ in protecting against CP-induced gastrointestinal dysfunction. Histopathological findings corroborated the biochemical results. Thus, NSO and TQ may prove clinically useful in amelioration of the intestinal toxicity associated with long-term CP chemotherapy.

AIM: To assess the hyperglycemia-induced microscopic changes in the posterior pituitary of streptozotocin (STZ) - induced diabetic adult albino rats. MATERIAL AND METHODS: After clearance from the Institutional Animal Ethical Committee, 36 animals were divided into six groups having six rats each: control, two weeks, one month, two months, four months and six months. Diabetes was induced with a single dose of streptozotocin administered through intraperitoneal route (60 mg/kg). Body weight and blood sugar were monitored at the biweekly interval. At the end of each experimental period, animals were euthanized by deep ether anesthesia and blood samples were collected by direct puncture of heart for biochemical analysis. Tissues were fixed in Karnovsky fixative and processed for paraffin sectioning. Routine and special stained sections were studied under the light microscope and relevant findings were recorded. RESULTS: Data obtained from biochemical analyses and histomorphometry along with the histopathological features revealed that with increasing duration of hyperglycemia was associated with increased serum creatinine and reduction in serum total protein; increased mean percentage of darkly stained large sized pituicytes and notable thickening of perisinusoidal collagen. CONCLUSION: It is therefore concluded that long-standing hyperglycemia which is associated with increased occurrence of predominantly large and darkly stained pituicytes and remarkably increased deposition of perisinusoidal collagen appear to be the important contributing factors somehow responsible for the derangement of the function of the posterior pituitary in chronic diabetes.

Introduction: Long-standing hyperglycemia in addition to many of its associated complications also hampers normal wound healing which may be further aggravated in the presence of infection and oxidative stress. Therefore, antioxidant supplementation appears to be strategically relevant for wound healing. This study is designed to explore the therapeutic potential of d-δ-tocotrienol rich fraction (d-δ-TRF) on skin wound healing in both healthy and diabetic rats. Materials and Methods: Diabetes was induced through single subcutaneous injection of alloxan at the dose of 100 mg/kg at hip region. 24 albino rats were divided into four groups; healthy control, diabetic control, healthy treated and diabetic treated. d-δ-TRF was administered to treated groups (200 mg/kg), orally, daily for 3 weeks. Full thickness excisional skin wounds were. Wound area was studied by assessing the morphological, histomorphological and histological features at weekly intervals and biochemical analyses were performed at the end of 3rd week. Results: The findings of present study revealed that d-δ-TRF accelerated the skin wound healing by means of early regeneration of both epidermal and dermal components; enhancement of serum protein synthesis, improvement of antioxidant status, maintenance of glycemic condition and controlling serum creatinine levels in diabetic rats. Conclusion: It is concluded that d-δ-TRF has significant therapeutic potency on the healing of skin wounds in both healthy and diabetics.

Introduction: Impaired wound healing events is a common complication in diabetes. One of the effective nutritional antioxidant on skin wound healing is vitamin E which contains saturated tocopherol and unsaturated tocotrienol forms. This present study is designed to explore the effect of different vitamin E isoforms on stitched skin wound in both healthy and diabetic rats. Materials and Methods: Forty eight albino rats were divided into eight groups; healthy control, diabetic control, healthy treated (d-α-tocopherol, d-δ-TRF and co-administrated) and diabetic treated (d-αtocopherol, d-δ-TRF and co-administrated). Diabetes was induced through single subcutaneous injection of alloxan at the dose of 100 mg/kg. Treated groups were administered d-a-tocopherol (200 mg/kg), d-δ-TRF (200 mg/kg) and co-administration (100 mg/kg of these two compounds each) orally and daily for three weeks. A horizontal skin incision was made on right mid-thigh region at 2.95 ± 0.17cm in length and wound was closed with an absorbable suture. Results: Histopathological and histomorphological results at the end of 3rd week revealed that the d-δ-TRF treated groups promote the regeneration and reorganization of epidermal and dermal components in healing of primary intention more effectively than the d-α-tocopherol and co-administrated groups. Conclusion: It is concluded that among different vitamin E isoforms the d-δ-TRF appears to be a more effective nutritional antioxidant on skin wound healing in both healthy and diabetics.

Sodium chlorate (NaClO3 ) is a widely used nonselective herbicide. It is also generated as a by-product during disinfection of drinking water by chlorine dioxide. The purpose of this study was to evaluate the effect of NaClO3 on rat intestine. Adult male rats were randomly divided into five groups: control and remaining four groups were administered orally different doses of NaClO3 and sacrificed 24 h after the treatment. The administration of NaClO3 produced acute oxidative stress in the intestine, which manifested in the form of markedly enhanced malondialdehyde levels and carbonyl content and lowered total sulfhydryl groups and glutathione levels. The activities of several brush border membrane (BBM) enzymes were greatly reduced as compared to control. There were alterations in the activities of various enzymes of carbohydrate metabolism and those involved in maintaining the antioxidant defense system. Histological studies support the biochemical results showing NaClO3 dose-dependent increase in tissue damage. Thus, the present study shows that oral administration of NaClO3 decreases the activities of BBM enzymes, induces oxidative stress, alters metabolic pathways, and impairs the antioxidant system of rat intestine. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1607-1616, 2017.

Sodium chlorate (NaClO3 ) is widely used in paper and pulp industries and as a non-selective herbicide. Humans can be exposed to NaClO3 through contaminated drinking water due to its improper and unchecked usage in industries and as herbicide. NaClO3 is also present as a major stable by-product in drinking water that has been disinfected with chlorine dioxide. In this study, we have investigated the effect of a single acute oral dose of NaClO3 on rat kidney. Adult male Wistar rats were divided into one control and four NaClO3 treated groups that were orally given different doses of NaClO3 and euthanized 24 hr after the treatment. Oral administration of NaClO3 resulted in increased hydrogen peroxide levels, lipid, and protein oxidation while thiol and glutathione content and activities of brush border membrane enzymes were decreased in kidney in a NaClO3 dose-dependent manner. Significant alterations in the activities of enzymes involved in carbohydrate metabolism and antioxidant defense were also observed. Administration of NaClO3 induced DNA fragmentation and increased DNA-protein cross-linking. Histological studies showed marked damage in kidney from NaClO3 treated animals. These results strongly suggest that NaClO3 induces nephrotoxicity via redox imbalance that results in DNA and membrane damage, metabolic alterations and brush border membrane enzyme dysfunction.

Although topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, topical delivery of siRNA for skin cancer treatment remains in its infancy. In the present study, the anticancer efficacy of a dendrosome-based formulation of polo-like kinase enzyme (PLK-1) specific siRNA was evaluated against DMBA induced skin papillomas in Swiss albino mice. The efficacy of the dendrosome based siRNA nano-formulation was evaluated on the basis of the effect on total numbers and sizes of tumor papillomas and the expression of apoptotic factors. The nano-formulation was successful in reducing the cumulative numbers as well as sizes of tumor nodules and causing significant apoptosis of skin tumor cells which led to better survival of the treated animals. The results indicate that dendrosomes are promising nanocarriers for the development of topical gene silencing approaches to treat skin tumors.

Highlights • NSO improves the endogenous antioxidant status and metabolic activity of liver. • NSO protects the liver against CP generated free radical attack. • Oral administration of NSO ameliorates the hepatotoxicity induced by CP treatment., Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO) can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally) with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism.

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Five week-old mice were divided into a vehicle control group, and groups exposed to ZnO nanoparticles at low (0.5 g/kg), middle (1 g/kg), high (3 g/kg), and exceptionally high-dose (5 g/kg). After the first, second, third, and fourth weeks’ of exposure, blood biochemistry, histopathology, and electron microscopic ultrastructural changes in liver, kidney and spleen were investigated. Increased alkaline phosphatase activities were observed in all treated mice being statistically significant at higher dose. No changes were observed in the serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, creatinine, blood urea nitrogen, and lipid levels. During the first and second weeks of the treatment, effects on the cytoarchitecture of liver, kidney, and spleen were not perceived while during the third and fouth weeks of treatment sporadic mild effects were seen. Ultrastructural electron microscopic changes in liver, kidney, and spleen were not observed for the low-dose group on the first, sec...

Four-week-old mice, weighing about 25-35 g were divided into five groups (8 mice in each group): vehicle control, low- (0.5 g/kg), middle- (1 g/kg), high- (3 g/kg), and exceptionally high-dose (5 g/kg). After first and second weeks of intraperitoneal exposure to AgNPs, biochemical, histopathological, and electron microscopic ultrastructural changes were investigated. No significant changes were observed in SGOT and ALP levels after first week of exposure, while the level of SGPT significantly increased (p

Considering the subdued efficacy of a single therapeutic modality in successful treatment of cancer, co-operative inhibition of cancer progression employing a combination of two or more therapeutic approaches is currently in vogue. An example of this strategy is the combination of chemotherapy and siRNA based therapy. However, development of delivery systems capable of successfully loading siRNA as well as a chemotherapeutic drug simultaneously and delivering both the cargos to the target site has been considered an uphill task. The present study demonstrates the development of an innovative poly-functional delivery system capable of loading siRNA and a chemotherapeutic drug concurrently and delivering the two payloads to the tumor site in a targeted manner. In the present study, liver cancer specific antibody conjugated PAMAM-dendrimer–siRNA complex functionalized and cisplatin loaded PLGA nanocomposites were developed. PAMAM dendrimers being cationic polymers facilitate binding of negatively charged siRNA. In this nanocomposite system (Ab@PAMAM–siRNA@Cis-PLGA NC), liver cancer specific antibody (Ab) serves the purpose of targeting the immuno-nanocomposite to the cells expressing liver cancer antigens; siRNA is the gene knockdown agent; cisplatin is the therapeutic anticancer-drug; PLGA NPs act as cisplatin delivery vehicle, provide a scaffold to dendrimer and also subdue its cytotoxicity; PAMAM acts as siRNA carrier and may facilitate endosomal escape. The promise of polyfunctional Ab@PAMAM–siRNA@Cis-PLGA NC to be used in cancer therapy was highlighted from the in vivo data enumerating synergistic anti-cancer effect of the two payloads resulting in enhanced apoptosis of cancer cells and augmenting survival of the treated animals.

Cis-Diamminedichloroplatinum II- (CP-) induced neurotoxicity is one of the least explored aspects of this drug. Dorsal root ganglia (DRG) cells are considered as the primary target, and their damage plays a vital role in pathogenesis and etiology of CP-induced neurotoxicity. The present study is aimed at confirming if riboflavin (RF) has any protective role in shielding the DRG from CP-induced toxicity. After conducting the established treatment strategy on mice under photoillumination, it was observed that, despite the fact that RF alone is partially toxic, its combination with CP significantly ameliorated the drug-induced damage in DRG cells as evidenced by histological analysis. In addition, it was interesting to observe that the combination group (RF + CP) was able to induce apoptosis in the target cells up to a significant extent which is considered as the most preferred way of countering cancer cells. Therefore, RF can act as an effective adjuvant compound in CP-based chemoradiotherapy to improve clinical outcomes in the contemporary anticancer treatment regimes.

Background: Non-steroidal anti-inflammatory drugs are very commonly used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet agent. They have significant adverse effect on liver and kidney besides damaging stomach. Their effect on liver and kidney are of serious concern. Hence, we have decided to study the preventive effect of Nigella sativa against paracetamol induced hepatic and renal damages. Methods: Ethanolic and aqueous extracts of N. sativa were prepared with the help of Soxhlet’s apparatus. Totally, 36 wistar albino rats (150-200 g) of either sex were divided into six groups of six each. Group I was administered with distilled water, Group II-VI were treated with paracetamol 750 mg/kg i.p. Group III-VI were test groups also treated with N. sativa aqueous extract (200 and 400 mg/kg p.o) and ethanolic extract (200 and 400 mg/kg p.o), respectively. The treatment was given daily for 7 days and on 8th all the rats were sacrificed and the blood was analyzed for hepatic and renal function tests and tissue was preserved for histopathological examination. Results: Paracetamol administration caused a marked hepatic and renal damage, which is evidenced by the increase in liver and renal function test parameters in the negative control group. N.sativa extracts prevented this damage. The protective was seen maximum in ethanolic extract followed by the aqueous extract in dose-dependent manner. Conclusion: Ethanolic extract showed significant protection against paracetamol-induced and renal damage.

Objectives : One of the common clinical observations regarding long-standing hyperglycemia is autonomic neuropathy, probably due to its unfavorable destructive effects on the neurons of the autonomic ganglia. Accordingly, the current study was aimed to analyze the effect of experimental hyperglycemia on parasympathetic pterygopalatine ganglion (PtG) and sympathetic coeliac ganglion (ClG) of albino rats. Methods: Thirty-six albino rats were divided into six groups (n=6, each) and were designated as control, two weeks, one month, two months, four months and six months groups. Diabetes was induced with a single dose of streptozotocin (STZ, 60 mg/kg, i.p.). Body weight and blood sugar were monitored at biweekly intervals. At the end of each experimental period, animals were euthanized by deep ether anesthesia and blood samples were collected by direct puncture of heart for biochemical analysis. Animals were perfused with Karnovsky fixative. After 48 hours, tissue samples were collected and processed for light microscopy. Results : Biochemical analysis of serum revealed increased serum creatinine and reduced serum total protein. Histopathology and histomorphometry of ganglia revealed that the progressively increasing duration of hyperglycemia was associated with decreased proportion of small-sized neurons, increased proportion of large-sized neurons, dark and dead neurons, and thickening of capsular and endoneurial collagen. Conclusion: The association of the long-standing hyperglycemia with increased neuronal death, altered proportion of neurons and deposition of collagen fibers in autonomic ganglia appear to be important contributing factors likely to be responsible for diabetic autonomic neuropathy.

Cisplatin (CP) is an effective anti-cancer drug which causes remarkable toxicity to the kidney, particularly to proximal tubules, by generating reactive oxygen species. Nigella sativa (NS), commonly known as "black cumin" reduces the progression of various kidney disorders. Thymoquinone (TQ), the major bioactive constituent of NS seeds, has been credited for various pharmacological effects of NS. Since, a typical clinical CP dosing regimen involves CP administration in multiple cycles over a long time duration, hence the present study aimed to evaluate the renoprotective efficacy of NS oil and TQ against multiple dose CP treatment induced deleterious biochemical and histological alterations in rat kidney. Adult male Wistar rats were divided into six groups viz. control, CP, CPNSO, CPTQ, NSO and TQ. Animals in CPNSO and CPTQ groups were pre-administered NSO (2ml/kg bwt, orally) and TQ (1.5mg/kg bwt, orally) respectively for 14 days and were then treated with CP (3mg/kg bwt, i.p), every fourth day for 20 days while still receiving NSO/TQ. NSO and TQ administration, prior to and along with CP treatment, attenuated CP induced renal functional impairment as evident by significantly restored serum creatinine and blood urea nitrogen levels. CP treatment alone led to significant decline in the specific activities of brush border membrane (BBM) marker enzymes viz. ALP (-46.64%), GGTase (-50.24%) and LAP (-42.15%), while NSO or TQ administration to CP treated rats significantly prevented the decline in the activities of these enzymes in isolated BBM vesicles (BBMVs) as well as in the homogenates of renal cortex and medulla. Furthermore, both NSO and TQ administration also mitigated the CP induced perturbations in renal metabolic and redox status. Histological studies supported these biochemical results showing significant attenuation of CP induced kidney damage in CPNSO and CPTQ cotreated groups. Thus, NSO and TQ have excellent scope for use as functional food or combinatorial nutraceuticals in CP chemotherapy to ameliorate the accompanying nephropathy in long term cancer chemotherapy.

It is the first report where different amounts of resol resin (RS) were incorporated with chitosan-hydroxyapatite (CHA) to develop a triconstituent nanoensemble CHA-RS(0.5,1,2), via simple co-precipitation method. The results of SEM, TEM, TGA and mechanical analysis revealed irregular interconnected rough morphology with homogenous distribution of needle shaped particles having average size ranging between 12 and 19nm, possessing higher thermal stability and mechanical strength, respectively relative to CHA (binary) nanocomposite. The CHA-1RS nanocomposite showed enhanced protein adsorption and ALP activity with excellent apatite formation ability compared to CHA-RS(0.5,2) and CHA nanocomposites. Thus, CHA-1RS nanocomposite was selectively tested as bare implant in the repair of critical-size calvarium defect (8mm) in albino rat. The histopathological and radiological investigations indicated that CHA-1RS prompted the bone regeneration ability as early as 2 weeks postimplantation demonstrating remarkably faster healing of calvarial defect relative to Cerabone. These findings have placed CHA-1RS on the pedestal to be employed as a potential alternative biomaterial for bone tissue engineering.

Clinical isolates (n = 55) of Pseudomonas aeruginosa were screened for the extended spectrum β-lactamases and metallo-β-lactamases activities and biofilm forming capability. The aim of the study was to demonstrate the antibiofilm efficacy of gum arabic capped-silver nanoparticles (GA-AgNPs) against the multi-drug resistant (MDR) biofilm forming P. aeruginosa. The GA-AgNPs were characterized by UV-spectroscopy, X-ray diffraction, and high resolution-transmission electron microscopy analysis. The isolates were screened for their biofilm forming ability, using the Congo red agar, tube method and tissue culture plate assays. The biofilm forming ability was further validated and its inhibition by GA-AgNPs was demonstrated by performing the scanning electron microscopy (SEM) and confocal laser scanning microscopy. SEM analysis of GA-AgNPs treated bacteria revealed severely deformed and damaged cells. Double fluorescent staining with propidium iodide and concanavalin A-fluorescein isothiocyanate concurrently detected the bacterial cells and exopolysaccharides (EPS) matrix. The CLSM results exhibited the GA-AgNPs concentration dependent inhibition of bacterial growth and EPS matrix of the biofilm colonizers on the surface of plastic catheters. Treatment of catheters with GA-AgNPs at 50 µg ml(-1) has resulted in 95% inhibition of bacterial colonization. This study elucidated the significance of GA-AgNPs, as the next generation antimicrobials, in protection against the biofilm mediated infections caused by MDR P. aeruginosa. It is suggested that application of GA-AgNPs, as a surface coating material for dispensing antibacterial attributes to surgical implants and implements, could be a viable approach for controlling MDR pathogens after adequate validations in clinical settings.

The antibacterial effect of AgNPs was investigated by determining MIC/MBC and growth kinetics assay. The lowest MIC/MBC was found to be in the range of 11.25-22.5 µg ml(-1) . The growth kinetics curve shows that 25 µg ml(-1) AgNPs strongly inhibits the bacterial growth. Confocal laser scanning electron microscopy (CLSM) shows that as the concentration of NPs increases, reduction in the number of cells was observed and at 50 µg ml(-1) of NPs, 100% death was noticed. Scanning electron microscopy (SEM) shows cells were severely damaged with pits, multiple depressions, and indentation on cell surface and original rod shape has swollen into bigger size. High resolution-transmission electron microscopic (HR-TEM) micrograph shows that cells were severely ruptured. The damaged cells showed either localized or complete separation of the cell membrane. The NPs that anchor onto cell surface and penetrating the cells may cause membrane damage, which could result in cell lysis. The interaction of AgNPs to membrane biomolecules; lipopolysaccharide (LPS) and L-α-phosphatidyl-ethanolamine (PE) were investigated by attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy. LPS and PE showed IR spectral changes after AgNPs exposure. The O-antigen part of LPS was responsible for interaction of NPs through hydrogen bonding. The phosphodiester bond of PE was broken by AgNPs, forming phosphate monoesters and resulting in the highly disordered alkyl chain. The AgNPs-induced structural changes in phospholipid may lead to the loss of amphiphilic properties, destruction of the membrane and cell leaking. The biomolecular changes in bacterial cell envelope revealed by ATR-FTIR provide a deeper understanding of cytotoxicity of AgNPs.

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

Background Nephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa , is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury. Objective The present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects. Results The effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2 ml/kg bwt. orally), prior to and following a single dose CP treatment (6 mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group. Conclusion The biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury.

Sodium chlorate (NaClO

Objective The present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits. Methods The cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n = 18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1 × 10 9 cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined. Results Groups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant ( p Conclusion Short-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). MRSA is an important pathogen in the healthcare sector that has neither been eliminated from the hospital nor community environment. In humans, S. aureus causes superficial lesions in the skin and localized abscesses, pyogenic meningitis/encephalitis, osteomyelitis, septic arthritis, invasive endocarditis, pneumonia, urinary tract infections and septicemia. Investigations focused in the search of other alternatives for the treatment of MRSA infections are in progress. Among the range of compounds whose bactericidal activity is being investigated, ZnO nanoparticles (ZnO-NPs) appears most promising new unconventional antibacterial agent that could be helpful to confront this and other drug-resistant bacteria. The aim of present study is to investigate the antibacterial potential of ZnO-NPs against Staphylococcus species isolated from the pus and wounds swab from the patients with skin and soft tissue infections in a tertiary care hospital of north India. ZnO-NPs (≈19.82 nm) synthesized by sol-gel process were characterized using scanning electron microscopy, X-ray diffraction , and Atomic force microscopy. The antibacterial potential was assessed using time-dependent growth inhibition assay, well diffusion test, MIC and MBC test and colony forming units methods. ZnO-NPs inhibited bacterial growth of methicillin-sensitive S. aureus (MSSA), MRSA and methicillin-resistant S. epidermidis (MRSE) strains and were effective bactericidal agents that were not affected by drug-resistant mechanisms of MRSA and MRSE.

ObjectiveTo explore the exact role of histamine receptors in respiratory system.MethodsThe cohort comprised of six groups (group I control and group II-VI treated) containing five rabbits in each group. Control-group received vehicle (sterile distilled water) and treated groups received subcutaneous histamine (100 μg/kg, b.i.d.), and H1R-agonist (HTMT), H2R-agonist (amthamine), H3R-agonist (R-(−)-α-methylhistamine) and H4R-agonist (clobenpropit) each in a dose of 10 μg/kg, b.i.d. for 30 subsequent days. After completion of treatment, animals were euthanized and perfused with 10% buffered formalin. Small tissue blocks of trachea and lungs were processed for paraffin embedding. Observations were recorded in sample photomicrographs taken from 10 μm thick. Haematoxylin and eosin stained sections.ResultsIt was observed that trachea and bronchi from histamine, H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general, cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells.ConclusionsIt is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy, hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.