Amirhossein Ahmadi

Ghasemali Khorasani

Maryam Ghasemi

Mohammad Azadbakht

Peyman Zamani

Seyed Jalal Hosseinimehr

English

HRČAK - Portal of Croatian Scientific and Professional Journals

Acta Dermatovenerol Croat               2010;18(1):2-7                           MEDICAL RESEARCHEffect of Aloe Cream versus Silver Sulfadiazine for Healing Burn Wounds in Rats Seyed Jalal Hosseinimehr1, 2, Ghasemali Khorasani3,4, Mohammad Azadbakht2,5, Peyman Zamani3, Maryam Ghasemi6, Amirhossein Ahmadi7 1Department of Medicinal Chemistry, Faculty of Pharmacy, 2Traditional and Complementary Medicinal Research Center, Mazandaran University of Medical Sciences, 3Department of Surgery, Faculty of Medicine, Mazandaran University of Medical Sciences, 4Department of Surgery, Faculty of Medicine, Tehran University of Medical Sciences, Tehran,  5Department of Pharmacogenosy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 6Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, 7Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran Corresponding author:Assist. Professor  Seyed Jalal Hosseinimehr, PhDFaculty of PharmacyMazandaran University of Medical SciencesSari, Iransjhosseinim@yahoo.com, sjhosseinim@mazums.ac.ir Received: October , 009Accepted: January 8, 010summary The management of burn injury remains a problem and it is the major cause of death and disability. The aim of this study was to evaluate the efficacy of Aloe vera cream in the treatment of thermal burn wounds and to compare these results with silver sulfadiazine in rats. Animals were divided into four groups. Animals were administered topical cream (Aloe vera powdered gel 0.5% and silver sulfadiazine) at 4 h of burn injury induced by hot water. On special days, according to study protocol, wound size was determined and skin sample histopathology performed in animal groups administered topical therapies. On day 5, the mean wound size was 5.5, 4, 0.78 and 4.1 cm in control, base, aloe and silver group, respectively. The wound size was significantly smaller in aloe group as compared with other groups. Histologic comparison showed aloe to increase reepithelialization in burn wounds significantly as compared with other cream-treated wounds. The results of this study showed aloe cream to significantly increase reepithelialization in burn wounds as compared with silver sulfadiazine.  Key words: burn, aloe vera, wound, silver sulfadiazineIntroduCtIon  Thermal burn injury is a major cause of death and disability, with high health care cost. Healing of burn wounds remains a challenge to modern medicine, although many antiseptics have been discovered. Burn management entails significant length of hospital stay, expensive medication, mul-tiple operative procedures and prolonged period of rehabilitation. This makes burn care an expensive proposition and every effort should be made to provide a shorter inpatient care for burn patients (1). We have recently shown that a significant number of patients exposed to thermal and boil-ing burn injury in northern Iran stay for long time at hospital for treatment. More than 60% stayed at ACTA DERMATOVENEROLOGICA CROATICAhospital between 8 and 0 days (). Silver sulfa-diazine (SSD) cream 1% is the most widely used topical treatment for burn injury. The antimicrobial efficacy of SSD is probably the main reason for the widespread use of this agent (). Delayed wound healing is the major clinical adverse effect of silver topical agent following treatment. The wound healing effects of SSD were studied with vaselinated tulle gras in burn patients. It was dem-onstrated that SSD delayed wound healing (4). Several adverse reactions and side effects have been reported, such as resistance to SSD, renal toxicity, and leukopenia, thus confirming that this topical cream should not be used for long periods on extensive wounds (4). Sloughing of dead tis-sue in partial thickness burns is retarded because SSD delays or prevents colonization by microor-ganisms. SSD might also slow down the healing of the wound (5). Prolonged application on partial-thickness burn wounds results in high patient care cost and complicates wound healing because in-patient follow up is needed. It is important to find more effective drugs with shorter time application. Aloe vera (family Liliaceae) has been used in traditional medicine for a long time. It is one of the most recognizable herbs in the world. The medici-nal parts are succulent leaves. Leaf gel, leaf juice, both fresh and dry aloe gel, obtained by breaking or slicing a leaf, is the principal part of the plant used in herbal medicine.   Topical skin gel provides excellent health sup-port for the skin. Aloe vera contains many impor-tant nutrients for the body, including amino acids, B vitamins, and other nutrients that support general health. It has many pharmacological properties in-cluding antioxidant, wound healing, antibacterial, antifungal and immunomodulating effects (6-1). Although burn wound healing was one of the ma-jor indications for use of Aloe vera gel in several animal and clinical studies, there are few studies comparing the efficacy of this gel and SSD in the treatment of burns in animals (8,14).  Realizing the potential use of Aloe vera gel in wound healing, the present study was undertaken to study the effect of Aloe vera gel cream in com-parison with SSD on the rate of burn wound heal-ing, i.e. burn wound size and reepithelialization.    materIals and methods Aloe vera Pure spray-dried Aloe vera powder was ob-tained from Zarban Phyto-Pharmaceutical Com-pany, Iran. These products consist of inner gel from plants; 150 g of Aloe vera powder were ob-tained from 30 L of gel filtered from the plant.  Preparation and formulation of aloe cream  Two grams of liquid white paraffin, 7.5 grams of sterile alcohol, 7.5 grams of acetyl alcohol,  grams of solid white paraffin, and propylene para-ben (0.015 g) were mixed and heated to boiling point as aqueous phase. Half gram of pollen saf-fron with 70 mL deionized water was added to the mixture of 7 grams of propylene glycol,  grams of sodium luryl sulfate and 0.05 grams of meth-yl paraben. The mixture was heated as organic phase. Then, two separate phases were mixed continuously while being treated to lower temper-ature. Thus, a uniform cream was produced and filled in tube after cooling down. The cream con-tained 0.5% of Aloe vera gel powder. Our exper-imental study and formulations were carried out under sterile conditions. The final creams were tested for any probable microbial contamination.  Study animals Male Wistar rats (n=48) weighing 180 to 00 grams were used and housed under standard con-ditions at room temperature and given laboratory food and water ad libitum throughout the study. The experimental protocol was approved by Eth-ics Committee of Mazandaran University of Medi-cal Sciences prior to commencement of the study. The weights of the animals were measured. They were anesthetized intraperitoneally with thiopen-tal (40 mg/kg body weight), while their backs were shaved. They were then placed in supine position inside the bottom of hot water (90 oC for 6 sec-onds). This heat exposure caused a uniform sec-ond-degree burn on the back of the skin. In this experiment, approximately 10% of total body sur-face (TBSA) was burned. The animals were re-suscitated with an intraperitoneal injection of 5 mL of normal saline solution.  After 4 h, the animals were assigned at random to four groups of 1 animals. Group 1 served as control group and no topical agent was applied; group  were treated with base cream (base cream without effective agent); group  were treated with 1% SSD (Behvarzan Pharma-ceutical Company, Rasht, Iran); and group 4 were treated with 0.5% powered Aloe vera cream. Treatment began 4 h after burn injury. Wounds were treated twice daily.  In order to quantify the rate of wound healing, the size of lesions was determined on days 1, , 7, 10, 14, 0 and 5 of burn injury. At this time, study Hosseinimehr et al.     Acta Dermatovenerol CroatThe effect of aloe on wound healing     010;18(1):-74 ACTA DERMATOVENEROLOGICA CROATICA010004050607080901007 10 14 20 25days after burn injury% wound burnControlBaseAloeSilveranimals were kept in good position and wound margin was traced on a transparent plastic sheet using a fine-tipped pen. The lesion body area was displayed as mm on each experimental day. The wound area on day 1 was considered as 100% and wound areas on subsequent days were com-pared with the initial wound area.  Histological study  Due to the wound healing of burn wounds, reepithelialization was evaluated after 5 days as the last day of treatment period. For this purpose, skin tissue samples were taken for histological studies with a small excision containing part of the wound area. Tissues were fixed in 10% formalin. Paraffin-embedded sections (5 µm thick) were prepared and stained with hematoxylin and eosin. Light microscopy was used to evaluate pathologi-cal changes, e.g., granulation tissue formation and reepithelialization in wounds and their comparison with normal tissue.  Statistical analysis  One-way analysis of variance (ANOVA) and Tukey post test were used on group compari-son. Differences were considered significant at P<0.05.   results  Wound condition on day 7 after burn was as-sessed clinically in all groups to facilitate exact determination of wound size. Skin lesions were measured on days 7, 14, 0 and 5 of burn in-jury and the ratio to day 1 was evaluated. The mean wound size on day 5 was 5.5, 4, 0.78 and 4.1 cm in the control, base, aloe and SSD group, respectively (Table 1). There were sig-nificant differences between aloe group and the other three groups (P<0.05). There was no statis-tically significant difference in wound size among the control, base and SSD groups on day 5 of treatment. The patterns of wound size ratios in the control and treatment groups are shown in Figure 1.  table 1. Mean wound size in control group and in base, aloe and silver sulfadiazine (SSD) cream treat-ed groups of animals Treatment group* Days after burn7 10 14 0 5 Control (cm) 8.9±.9 6.7±5.6 1±8 7.5±4 5.5± Base (cm) 8.4±8. 5.±6 1.±5.6 6.8±. 4±. Aloe (cm) 0.4 ±5.8 17.4 ±. 5.±5.7 1.8±1.5 0.78 ±1.** SSD (cm) 4±4.4 8±6 18.6±8.5 6.6±.7 4.1±.6 *Values are means ± SD for each group of animals; **P<0.05 comparison of aloe extract cream compared to other groups.Figure 1. Comparison of wound burn size in control, base, Aloe vera and silver sulfadiazine treated groups. The wound size measured on day 7 was considered as initial and wound size on other days was calculated against this initial value. Hosseinimehr et al.     Acta Dermatovenerol CroatThe effect of aloe on wound healing     010;18(1):-75ACTA DERMATOVENEROLOGICA CROATICA 2Figure 3 Results of histological studies indicated an im-provement in wound healing on day 5 of treat-ment. The slides from aloe treated burned skin biopsies showed significant wound healing by reepithelialization of the epidermis and fibrosis of the dermis. The inflammation and granulation tissue formation were minimal and bacteria were not found in this specimen (Fig. ). The specimens of SSD treated wounds showed a lesser degree of wound healing as compared with aloe treated group according to reepithelialization of the der-mis, fibrosis of the dermis with more ulceration, granulation of tissue formation and inflammation (Fig. ). The slides of wounds treated with basic creams showed a lesser degree of wound heal-ing compared to saffron and SSD treated groups. Bacteria were found in the wound treated with ba-sic creams. Histological samples of non-treated control group showed negligible wound healing and many bacteria in the specimen. Macroscopic images of burned rats are shown in Figure .dIsCussIon  Our findings demonstrated Aloe vera cream to have burn wound healing effects in rats. Heal-ing parameters showed aloe to be very effective in healing of burn injury; these effects were ob-served in the size of wound healing and on his-topathology. Although other studies showed aloe gel to be effective in wound healing in animal mod-els (8,14), they did not compare it with SSD as a common topical cream for burn injury. Our stud-ies showed aloe to be more effective than SSD in healing partial burn in rat. The antimicrobial effect is the major mechanism of SSD in wound heal-ing. The silver ion binds to the organism DNA and consequently releases the sulfonamide that kills the microbes (15). However, topical administration of SSD may be associated with hepatic and renal toxicity. These side effects were observed in the treatment of extensive burns (16,17). Although sil-ver-coated dressing acticoat has advantages over topical SSD, it also induced adverse reactions in patients (18).   1Figure 2  1Figure 2  1Figure 2  1Figure 2 ABCDFigure 2. Photomicrograph of the rat skin wound section on day 5 day in control (A) and base treated (B), Aloe vera treated (C) and silver sul-fadiazine treated (D) groups. Specimens were stained with hematoxylin and eosin.Figure 3. Visualization of burned rats from control (A), silver sulfadiazine treated (B) and aloe (C) cream treated groups on day 0.A CBHosseinimehr et al.     Acta Dermatovenerol CroatThe effect of aloe on wound healing     010;18(1):-76 ACTA DERMATOVENEROLOGICA CROATICA Wound healing involves several biological pro-cesses such as inflammation and granulation tis-sue formation. Collagen is the major protein of the extracellular matrix and provides strength and in-tegrity to the dermis and other supporting tissues (19-1). Aloe vera application has been indicated to increase the content of collagen (0). Glyco-protein fraction is the major component of aloe involved in its wound healing effect through cell proliferation and migration (). Isolated glyco-protein fraction promoted growth of dermal fibro-blasts, as compared with neutral polysaccharide fraction that exhibited no such effects (). The anti-inflammatory effects of aloe can contribute to resolving the inflammatory process induced by burn injury (). In this study, we observed that the aloe treated skin showed no bacteria in the biopsy specimen, while bacteria were found in the base cream treated skin. Infection is the main problem in the skin involved by burn injury; topical antimicro-bial reduces burn compliance. SSD is effective in this mechanism. Aloe gel has antimicrobial effects (10,1) and can result in wound healing and re-ducing infection in burn injury. Muller et al. showed that wound contraction was delayed by SSD. Aloe vera, when added to SSD, reversed this effect and wound half-life, and healing times were shortest in the SSD/Aloe vera groups and longest in the 1% SSD group. These data showed Aloe vera to have synergistic effects in wound healing in comparison to SSD alone (14).  In this study, we showed that aloe cream was effective in wound healing in burn animals. ConClusIon The size of skin lesion was smaller in saffron treatment as compared to SSD. The process of reepithelialization was more efficient in aloe treat-ed animals than in SSD treated animals. The an-timicrobial, cell proliferation and inflammatory ef-fects may be the mechanism of aloe action in burn healing.   references 1.   Gore MA, Akholekar D. Evaluation of bana-na leaf dressing for partial-thickness burn wounds. Burns 00;9:487-9. .   Khorasani G, Hosseinimehr SJ, Eghbalian A. Epidemiology and mortality of burns in the north of Iran. Res J Biol Sci 007;:519-..   Vloemans AFPM, Soesman AM, Suijker M, Kreis RW, Middelkoop E. A randomized clini-cal trial comparing a hydrocolloid-derived dressing and glycerol preserved allograft skin in the management of partial thickness burn. Burns 00;9:70-10. 4.   Atiyeh BS, Costagliola M, Hayek SN, Dibo S. Effect of silver on burn wound infection con-trol and healing: review of the literature. Burns 007;:19-48. 5.   Klasen HJ. A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns 000;6:11-8. 6.   Hu Q, Hu Y, Xu J. Free radical-scavenging activity of Aloe vera (Aloe barbadensis Miller) extracts by supercritical carbon dioxide ex-traction. Food Chem 005;91:85-90. 7.   Maenthaisong R, Chaiyakunapruk N, Nirunt-raporn S, Kongkaew C. The efficacy of Aloe vera used for burn wound healing: a systema-tic review. Burns 007;:71-8. 8.   Rodriguez-Bigas M, Cruz NI, Suarez A. Com-parative evaluation of Aloe vera in the mana-gement of burn wounds in guinea pigs. Plast Reconstr Surg 1988;81:86-9. 9.   West DP, Zhu YF. Evaluation of Aloe vera gel gloves in the treatment of dry skin associated with occupational exposure. Am J Infect Con-trol 00;1:40-. 10. Agarry OO, Olaleye MT, Bello-Michael M. Com-parative antimicrobial activities of Aloe vera gel and leaf. Afr J Biotechnol 005;4:141-4.11. Rosca-Casian O, Parvu M, Vlase L, Tmas M. Antifungal activity of Aloe vera leaves. Fitote-rapia 007;78:19-. 1. Chow JTN, Williamson DA, Yates KM, Goux WJ. Chemical characterization of the immuno-modulating polysaccharide of Aloe vera Car-bohyd Res 005;40:111-4. 1. Habeeb F, Shakir E, Bradbury F, Cameron P, Taravati MR, Drummond AJ, et al. Screening methods used to determine the anti-microbi-al properties of Aloe vera inner gel. Methods 007;4:15-0. 14. Muller MJ, Hollyoak MA, Moaveni Z, Brown LH, Herdon DN, Heggers JP. Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin. Burns 00;9:84-6. 15. Ulkur E, Oncul O, Karagoz H, Celikoz B, Ca-vuslu S. Comparison of silver-coated dressing (acticoat), chlorhexidin acetate 0.5% (bac-tigrass), and silver sulfadiazine 1% (silverdin) Hosseinimehr et al.     Acta Dermatovenerol CroatThe effect of aloe on wound healing     010;18(1):-77ACTA DERMATOVENEROLOGICA CROATICAfor topical antibacterial effect in Pseudomonas aeruginosa-contaminated, full-skin thickness burn wounds in rats. J Burn Care Rehabil 005;6:40-. 16. Chaby G, Viseux Y, Poulain V, De Cagny B, Denoeux JP, Lok C. Topical silver sulfadiazi-ne-induced acute renal failure. Ann Dermatol Venereol 005;1:891-. 17. Fraser JF, Cuttle L, Kempf M, Kimble R. Cy-totoxicity of topical antimicrobial agents used in burn wounds in Australia. Aust N Z J Surg 004;74:19-4. 18. Trop M, Novak M, Rodl S, Hellbom B, Kroell W, Goessler W. Silver-coated dressing acti-coat caused raised liver enzymes and argy-ria-like symptoms in burn patient. J Trauma 006;60:648-5. 19. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe vera on the glycosaminogly-cans in the matrix of healing dermal wounds in rats. J Ethnopharmacol 1998a;59:179-86. 0. Chithra P, Sajithlal GB, Chandrakasan G. In-fluence of Aloe vera on the healing of dermal wounds in diabetic rats. J Ethnopharmacol 1998b;59:195-01. 1. Chithra P, Sajithlal GB, Chandrakasan G. In-fluence of Aloe vera on collagen characteris-tics in healing dermal wounds in rats. Mol Cell Biochem 1998c;181:71-6. . Chol SW, Son BW, Son YS, Park YI, Lee SK, Chung MH. The wound-healing effect of a gly-coprotein fraction isolated from Aloe vera. Br J Dermatol 001;145:55-45. 23. Krishnan PK. The scientific study of herbal wound healing therapies: current state of play. Curr Anaesth Crit Care 006;17:1-7. Hosseinimehr et al.     Acta Dermatovenerol CroatThe effect of aloe on wound healing     010;18(1):-7Alga - known medicine against rheumatic as well as other kind of pain; year 194.(From the collection of Mr. Zlatko Puntijar) 

Effect of Aloe Cream versus Silver Sulfadiazine for Healing Burn Wounds in Rats

Abstract

Similar works

Full text

Available Versions

HRČAK - Portal of Croatian Scientific and Professional Journals