Papers by Dr. Rohit Dhumal
Objective: The present investigation describes in vivo dermal absorption and sub acute dermal tox... more Objective: The present investigation describes in vivo dermal absorption and sub acute dermal toxicity (28 days) study of essential oil from Blumea eriantha DC (Compositae). Methods: The essential oil was extracted by hydrodistillation using Clevenger type apparatus. The dermal absorption studies were conducted in rabbits at dose of 15% (v/v) while sub acute toxicity was carried out in adult Holtzman rats at doses of 3%, 9% and 15% (v/v). The in vivo dermal absorption of essential oil was examined by means of Head space GC MS. Results: The in vivo dermal absorption did not show presence of any essential oil component in the rabbit plasma samples. Further the sub acute treatment with essential oil did not show significant differences in the body weight, food consumption, hematological and biochemical parameters examined in both female and male groups. Necropsy and histopathological examination did not reveal any treatment related changes in treated groups. However, during the first w...
Data File 1: Toxicity study in rat model Data File 2: Behavioural study in zebrafish model
Journal of Ethnopharmacology, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Indian journal of medical research, 2017
Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbona... more Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 μg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 μg/kg BW/day groups...
RSC Advances, 2017
Bone grafts made from nanofibrous polycaprolactone loaded with bone-mimicking ceramic hydroxyapat... more Bone grafts made from nanofibrous polycaprolactone loaded with bone-mimicking ceramic hydroxyapatite or hardystonite showed efficient bone healing in anin vivorat skull defect model.
Asian Pacific Journal of Reproduction, 2014
ABSTRACT Objective To evaluate the safety & efficacy of Maa-Lact granules for its galacto... more ABSTRACT Objective To evaluate the safety & efficacy of Maa-Lact granules for its galactogougue activity in Holtzman rats and its effect on suckling pups. Methods Group I rats were treated as control, group II and III rats were treated with 500 mg/kg, 1 000 mg/kg of Maa-Lact granules for 21 days. Weekly body weights of dams and pups were collected, litter survivability for 22 days and ocular blood samples were collected on 1st day of parturition and 21st day of post parturition for the estimation of prolactin levels. On 21st day blood samples were collected from retro-orbital sinus for haemotological and biochemical estimations. On the same day of weaning rats were sacrificed and subjected to necropsy and individual organ weights were recorded. Results No significant difference in weekly food weight consumption, body weights between control & treated groups with normal clinical signs. There is no mortaly in dams throught the study period with no significant difference in pups weights. The percentage mortality in pups was 14.43 %, 14.07 %, and 13.42% in group I, group II and group III, respectively. The histopathological finding has shown that treated groups have less convulution and adipose tissue deposition along with increase in length and branching of lactiferous duct and alveolar size. Conclusion Based on above results, it can be concluded that Maa-Lact posseses significant galctogogue activity.
Drug Delivery and Translational Research, 2013
In vivo biocompatibility of nanofibrous poly-L-lactic acid (P), poly-L-lactic acid/gelatin (PG), ... more In vivo biocompatibility of nanofibrous poly-L-lactic acid (P), poly-L-lactic acid/gelatin (PG), poly-L-lactic acid/hydroxyapatite (PH), and poly-L-lactic acid/gelatin/hydroxyapatite (PGH) scaffolds, useful in regenerative medicine and drug delivery, was evaluated by subcutaneous implantation in both male and female rats (n = 5) for up to 90 days. The body weight of each animal in the study was evaluated on a weekly basis, and no significant difference was noticed. Total and differential leukocyte counts displayed no inflammatory reaction due to scaffold implantation. Gross observation and histology of necropsied vital organs exhibited normal morphology of cell types and tissue, denying any systemic adverse reaction on distal organs. Histology of subcutaneous tissue surrounding scaffolds was done to assess any local toxic effect of implants and found all scaffolds to be compatible and nontoxic. Moreover, no remnant of scaffolds was observed in any of the histological sections, suggesting all scaffolds to be biodegradable. All the results in this study confirm that nanofibrous scaffolds P, PG, PH, and PGH are biocompatible and safe for bone tissue engineering application.
Drug Delivery and Translational Research, 2013
Nanoparticles, being small (&... more Nanoparticles, being small (<1,000 nm) in size, provide high surface area-to-volume ratio as compared with the bulk materials which increase the concern about their potential toxicities. The present investigation was undertaken to evaluate the genotoxic potential of asymmetric lipid polymer hybrid nanoparticles of doxycycline hydrochloride (DH lipomer) following intravenous route. DH lipomer was prepared by modified nano-precipitation method as reported earlier. Doxycyline loading was found to be 20 ± 2.5 %. Average particle size of DH lipomer and blank lipomer was 512 ± 8 and 520 ± 6 nm, respectively. Micronucleus (MN) assay was performed in adult healthy Swiss mice whereas chromosomal aberration (CA) test and comet assay were performed in healthy Holtzman rats following intravenous administration. Animals were divided into two sets, male and female, each set comprising of six groups (n = 5/group), viz., three test groups, blank lipomer (BL), vehicle control (VC), and positive control. Groups treated with 1.5 mg/kg BW DH lipomer did not show micronuclei formation in bone marrow cell, DNA damage, and CA, respectively, as compared with VC, suggesting no genotoxicity. On the other hand 3 and 6 mg/kg BW revealed significant (P > 0.001) increase in micronuclei formation, DNA damage, and chromosomal aberrations. Furthermore, BL (6 mg/kg BW) did not reveal genotoxic response in any of the tests, suggesting lipomer components as non-genotoxic. No sex-dependent variation in genotoxicity was observed. This study therefore suggests the potential safety of the proposed dose of DH lipomer at 1 mg/kg BW. An interesting highlight of the study is safety of lipomer matrix which could be exploited for other biomedical application.
Toxicology International, 2013
Objective: The present study was undertaken to determine target organ safety of "Immuforte" to es... more Objective: The present study was undertaken to determine target organ safety of "Immuforte" to establish relationship between dose or exposure and response and also to identify potential parameters for monitoring adverse effects of "Immuforte" in clinical studies, if any. Materials and Methods: A total of 40 males and 40 females were randomly assigned to the four groups, namely group I (vehicle control; gum acacia), group II (120 mg/kg BW of Immuforte in gum acacia), group III (360 mg/kg BW of Immuforte in gum acacia), and group IV (600 mg/kg BW of Immuforte in gum acacia) consisting of 10 males and 10 females in each group. Additionally, a recovery group (600 mg/kg BW of Immuforte in gum acacia) containing 5 males and 5 females was included. Results: The results showed significant decrease in percent lymphocyte count of high and mid dose groups as compared to control group. The percent neutrophil counts in all the three treated groups of male and female rats were found to be significantly higher than that of control group (P < 0.05). In females MCV values in low dose and mid dose were significantly higher as compared to control (P < 0.05). The males from low dose group showed significant decrease in total serum protein, globulin, electrolytes, direct bilirubin, creatinine levels, whereas in mid dose group along with albumin, globulin. A significant decrease in AST and cholesterol was observed. In females, significant decrease was observed in total protein and globulin of low dose and mid dose of Immuforte-treated rats (P < 0.05). Though few hematological and biochemical parameters were different from control group, no does related response was observed and further, all these values were comparable with historical control data of the colony. Terminal body weight, organ weight, gross, and histopathology did not reveal any toxicity-related any adverse effects. Heavy metal analysis of the blood samples collected from terminally sacrificed animals did not show presence of heavy metals viz. lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As). Conclusion: The results of the present study demonstrated that Immuforte does not cause any observable toxicity at doses used in the study when administered for the period of 90 days and is safe for the human use and thus, Immuforte could be used safely for therapeutic use in humans.
Journal of Pharmaceutical Sciences, 2010
The present investigation involved preparation of hydrogel nanoparticles using a combination of h... more The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration.
Journal of Biomedical Nanotechnology, 2013
We studied the in vivo performance of scaffolds consisting of nanofibrous poly(L-lactic acid) (P)... more We studied the in vivo performance of scaffolds consisting of nanofibrous poly(L-lactic acid) (P) and blend of poly(L-lactic acid/gelatin) (PG) prepared by electrospinning and further composited them with hydroxyapatite (HA) via alternate soaking method, to get poly(L-lactic acid)/hydroxyapatite (PH) and poly(L-lactic acid)/gelatin/hydroxyapatite (PGH) scaffolds respectively. The purpose of this study was to assess and compare bone regeneration potential of electrospun P, PG and electrospun-alternate soaked PH and PGH scaffolds using rat as an animal model by creating two 5 mm circular defects in calvaria. The respective scaffolds were implanted into the defects as one side implantation and both side implantation. Defects left empty served as a negative control for one side implantation and as sham control for both side implantations. The outcomes of the scaffold implantation were determined after 6 and 10 weeks by digital radiography, micro-CT, dual-energy X-ray absorptiometry (DEXA) and histological analysis. PGH scaffold regenerated maximum amount of new bone with high bone mineral density (BMD) into the defects and complete closure occurred in just 6 weeks while other scaffolds failed to close the defects completely. PGH group exhibited highest BMD value after 10 weeks. Histological findings showed abundant osteoblasts and initiation of matrix mineralization in HA containing scaffolds. Masson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s trichrome staining showed collagen deposition in all scaffold groups except sham control group. Biochemical and haematological parameters were well with in normal range, indicating no infection due to scaffold implantation. These results prove PGH scaffold as a potential biomaterial for bone regenerative medicine.
Journal of Ayurveda and Integrative Medicine, 2013
Background: Reverse pharmacology for drug development has been highly productive and cost-effecti... more Background: Reverse pharmacology for drug development has been highly productive and cost-effective in recent past as it is based on the documented therapeutic effects of plants in ancient texts. Afrodet Plus ® is formulated for the treatment of male infertility, which contains ancient herbo-minerals. Its effi cacy and safety are validated through this animal study in reverse pharmacology mode. Objectives: This study was undertaken to evaluate effi cacy and safety of an Ayurvedic formulation Afrodet Plus ® in adult male rats. Materials and Methods: Twelve male rats (Holtzman) between 8 and 10 weeks of age were randomly selected and animals were assigned to a control and two treatment groups. Dosing was performed daily. Various parameters such as weekly body weight, hematology, serum testosterone levels, epididymal sperm count, and effi ciency of Daily Sperm Production (DSP) were evaluated. Results: It was found that epididymal sperm count had signifi cantly increased in both low-dose (+27.39%) and high-dose (+40.5%) groups as compared to control group. The DSP also showed an increase of 43.7% at high dose of 180 mg/kg body weight as compared to the control group. An increase in sperm motility and especially progressive motility was observed when evaluated by Computer Assisted Semen Analyzer. Histological evaluation of testicular tissue for spermatogenic index revealed that the index had increased in treatment group as compared to control group. Conclusion: This study revealed that oral administration of Afrodet Plus® resulted in signifi cant increase in DSP in the testis along with increase in epididymal sperm count and progressive motility as compared to control group without producing any treatment-related adverse effects. These fi ndings provide the documentary evidence that the use of Afrodet Plus® at 90 and 180 mg/kg body weight is effective and safe for the treatment of male infertility especially to improve sperm count and progressive motility.
Food and Chemical Toxicology, 2010
Research in nanotoxicology is still in nascent stages. This hampers the design of appropriate reg... more Research in nanotoxicology is still in nascent stages. This hampers the design of appropriate regulatory policies for these beneficial nano-drug delivery systems thus affecting their routine employment as therapeutics. Establishing the entire toxicological profile is thus indispensable for proving the human safety of nanocarriers, which was the primary objective of the current investigation. The developed curcumin loaded polymeric nanoparticles of Eudragit S100 were subjected to various toxicological evaluations which included acute-toxicity study, sub-acute-toxicity study (28 days) and various genotoxicity studies like in vivo Micronucleus assay, in vivo Chromosomal Aberration assay and in vivo Comet assay. The formulation was found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of curcumin in the acute-toxicity study. Sub-acute-toxicity study proved the safety of the formulation for prolonged administration at the commonly used therapeutic dose of 100mg/kg of body weight of curcumin and at twice the therapeutic dose. Genotoxicity studies proved the cellular safety of the developed formulation at the therapeutic dose, and even at doses equivalent to thrice the therapeutic dose. Thus the developed curcumin loaded polymeric nanoparticles of Eudragit S100 were found to be safe for oral administration for a short as well as a prolonged duration.
Materials Today Communications, 2021
Abstract Critical size calvarial bone defects and their repair is the major challenge in orthopae... more Abstract Critical size calvarial bone defects and their repair is the major challenge in orthopaedic surgery. Bone tissue engineering using varied combinations of scaffolds, stem cells, and growth factors is an emerging choice of treatment for variety of bone defects. Present study aimed to compare and evaluate the potential of poly e-caprolactone (PCL), PCL- graphene oxide (GO), PCL-GO-Cissus quadrangularis (CQ), and human umbilical cord-derived mesenchymal stem cells (hUCMSCs) seeded PCL (PCL- hUCMSCs), PCL-GO-CQ-hUCMSCs scaffolds to heal critical size calvarial bone defect in the rat models. Healthy adult Wister female rats (N = 30) with average body weight of 350 ± 30 g were divided to 6 groups with five animals in each group. Single critical size calvarial defects of 8 mm were created in the skull of each rat and same were treated with respective scaffolds. The outcome of the treatments was evaluated at 6 weeks and 12 weeks in terms of weight, haematological parameters and biochemical parameters for biocompatibility. New bone regeneration/healing was analysed using digital radiography and micro-computed tomography. Quality of bone formed was analysed by bone mineral density. Histological analysis of the bone tissues was performed using an optical microscope. All the scaffolds were biocompatible and there was no adverse effect of these scaffolds on animals. Higher bone regeneration was observed after 12 weeks of transplantation than 6 weeks. However, PCL-GO-CQ-hUCMSCs scaffolds exhibited highest bone regeneration 12 weeks post-transplantation. The unique combination of PCL-GO-CQ-hUCMSCs scaffold proved to be beneficial in bone regeneration by aiding nearly complete healing of defect site. Further studies with PCL-GO-CQ-hUCMSCs could pave the way for human clinical trials.
Journal of biomedical nanotechnology, 2011
The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthe... more The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthesized for the treatment of Brucellosis to increase efficacy of the drug. The present study was undertaken to determine the intravenous safety of blank lipomer and Lipomer DH in terms of maximum tolerated dose in rats. It was observed that blank lipomer and lipomer DH were safe when administered intravenously at doses 2000 mg/kg Bw and 18 mg/kg bw respectively.
Asian Pacific Journal of Reproduction, 2014
Toxicology International, 2013
The present study was undertaken to determine target organ safety of &amp;amp;amp;amp;amp;amp... more The present study was undertaken to determine target organ safety of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Immuforte&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; to establish relationship between dose or exposure and response and also to identify potential parameters for monitoring adverse effects of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Immuforte&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in clinical studies, if any. A total of 40 males and 40 females were randomly assigned to the four groups, namely group I (vehicle control; gum acacia), group II (120 mg/kg BW of Immuforte in gum acacia), group III (360 mg/kg BW of Immuforte in gum acacia), and group IV (600 mg/kg BW of Immuforte in gum acacia) consisting of 10 males and 10 females in each group. Additionally, a recovery group (600 mg/kg BW of Immuforte in gum acacia) containing 5 males and 5 females was included. The results showed significant decrease in percent lymphocyte count of high and mid dose groups as compared to control group. The percent neutrophil counts in all the three treated groups of male and female rats were found to be significantly higher than that of control group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In females MCV values in low dose and mid dose were significantly higher as compared to control (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The males from low dose group showed significant decrease in total serum protein, globulin, electrolytes, direct bilirubin, creatinine levels, whereas in mid dose group along with albumin, globulin. A significant decrease in AST and cholesterol was observed. In females, significant decrease was observed in total protein and globulin of low dose and mid dose of Immuforte-treated rats (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Though few hematological and biochemical parameters were different from control group, no does related response was observed and further, all these values were comparable with historical control data of the colony. Terminal body weight, organ weight, gross, and histopathology did not reveal any toxicity-related any adverse effects. Heavy metal analysis of the blood samples collected from terminally sacrificed animals did not show presence of heavy metals viz. lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As). The results of the present study demonstrated that Immuforte does not cause any observable toxicity at doses used in the study when administered for the period of 90 days and is safe for the human use and thus, Immuforte could be used safely for therapeutic use in humans.
Journal of Pharmaceutical Sciences, 2010
The present investigation involved preparation of hydrogel nanoparticles using a combination of h... more The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration. ß
Journal of Biomedical Nanotechnology, 2011
The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthe... more The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthesized for the treatment of Brucellosis to increase efficacy of the drug. The present study was undertaken to determine the intravenous safety of blank lipomer and Lipomer DH in terms of maximum tolerated dose in rats. It was observed that blank lipomer and lipomer DH were safe when administered intravenously at doses 2000 mg/kg Bw and 18 mg/kg bw respectively.
Journal of Ayurveda and Integrative Medicine, 2013
Reverse pharmacology for drug development has been highly productive and cost-effective in recent... more Reverse pharmacology for drug development has been highly productive and cost-effective in recent past as it is based on the documented therapeutic effects of plants in ancient texts. Afrodet Plus(®) is formulated for the treatment of male infertility, which contains ancient herbo-minerals. Its efficacy and safety are validated through this animal study in reverse pharmacology mode. This study was undertaken to evaluate efficacy and safety of an Ayurvedic formulation Afrodet Plus(®) in adult male rats. Twelve male rats (Holtzman) between 8 and 10 weeks of age were randomly selected and animals were assigned to a control and two treatment groups. Dosing was performed daily. Various parameters such as weekly body weight, hematology, serum testosterone levels, epididymal sperm count, and efficiency of Daily Sperm Production (DSP) were evaluated. It was found that epididymal sperm count had significantly increased in both low-dose (+27.39%) and high-dose (+40.5%) groups as compared to control group. The DSP also showed an increase of 43.7% at high dose of 180 mg/kg body weight as compared to the control group. An increase in sperm motility and especially progressive motility was observed when evaluated by Computer Assisted Semen Analyzer. Histological evaluation of testicular tissue for spermatogenic index revealed that the index had increased in treatment group as compared to control group. This study revealed that oral administration of Afrodet Plus(®) resulted in significant increase in DSP in the testis along with increase in epididymal sperm count and progressive motility as compared to control group without producing any treatment-related adverse effects. These findings provide the documentary evidence that the use of Afrodet Plus(®) at 90 and 180 mg/kg body weight is effective and safe for the treatment of male infertility especially to improve sperm count and progressive motility.
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Papers by Dr. Rohit Dhumal