BPC-157 in the genitourinary system. Peptide therapy in renal disease.

Abstract: The action of BPC-157 in the urogenital system plays a role both in preventive and nephroprotective treatment, but also contributes to alleviating already developed disease states and their symptoms.

Keywords: urinary system; reproductive system; urogenital system; kidney; ureter; urinary bladder; pelvis; uterus; rectum; urethra; kidney stones; vesicovaginal fistula; giant ureter; urinary incontinence; BPC-157 peptide therapy; experimental studies; method; ureteral stenosis; scrotal injury; nephroprotection; disease

List of abbreviations: BPC-157 – Body Protection Compound; LPP – Leak Point Pressure – intravesical pressure level;

Material and methods: Studies were conducted on laboratory animals, in this case male and female albino rats.

The urogenital system

Structure of the urogenital system

The most important element of the urinary system structure is the kidneys, which are paired organs whose parenchyma is formed from nephrons. Due to strong vascularization, a renal artery branches off from each kidney, dividing into upper, middle and lower branches. The kidneys are composed of medulla and cortex, from which papillae enter the minor calyces and then into the renal pelvis, forming the next structural element of the system – the ureters. The ureters connect the kidneys with the urinary bladder, which is a reservoir located in the pelvis with a pubic symphysis at the rear, while its front part differs depending on sex. In the female urogenital system, the uterus is located in front of the bladder, while in the male the rectum is. Urine accumulated in the bladder is excreted through the urethra, which in the male system is longer than in the female, and in both cases the urethra connects with the genitals, giving rise to the urogenital system. The structure of the urinary system also includes interlobar arteries transitioning into arcuate arteries. Let us illustrate the structure of the female and male urogenital system. (Fig. 1)

Figure 1. Structure of the male and female urogenital system

Functions of the urogenital system

The main function of the urinary system is considered to be the excretion from the body of all unnecessary and harmful metabolic waste products, which is why it can also be called the excretory system. Furthermore, it participates in hormone production and maintains a constant level of bodily fluids. The basic function of the reproductive system is reproduction through the production of gametes and egg cells. The male reproductive organs serve primarily to produce semen containing sperm, while the female organs serve to produce egg cells and hormones, additionally creating conditions for fertilization and fetal development in the maternal body.

Diseases of the urogenital system

The human urogenital system is particularly sensitive and susceptible to infections, which is why prevention of diseases of this system is so important. Untreated diseases of the urogenital system can lead to serious consequences and complications such as infertility, and in extreme cases can be life-threatening. To avoid disease and prevent its aggravation, regular basic urine tests are important, as well as preventive therapy to protect the urogenital system from all types of infections and diseases, especially since they often have no initial symptoms, which complicates diagnosis and delays treatment. A modern method in the treatment of urogenital conditions and diseases is BPC-157 therapy.

BPC-157 peptide therapy for selected urogenital conditions

1. Urinary incontinence

Urinary incontinence refers to a process in which urine leakage is uncontrolled and involuntary, occurring during, among other things, coughing, sneezing or physical exertion. In the general classification, several degrees of urinary incontinence are distinguished depending on the amount of uncontrolled urine leakage, including droplet, mild, moderate, severe and very severe degrees. The most common cause of urinary incontinence complaints is considered to be weakening of the pelvic floor muscles, which are responsible for tightening the urethra and controlling urination. Symptoms occur in both women and men, however in women they occur more frequently due to procedures and operations performed in the pelvic area, natural childbirth or hormonal changes. In men, urinary incontinence most commonly occurs due to enlargement of the prostate gland. The condition can coexist with other diseases such as diabetes, Ehlers-Danlos syndrome or chronic constipation. Pharmacological treatment is used in cases of urge urinary incontinence and involves anticholinergic medications. Surgical treatment is most commonly used in cases of stress urinary incontinence, including through the implantation of an artificial sphincter. Conservative treatment involves, for example, electrostimulation of the pelvic floor muscles or Kegel muscle exercises, i.e. pelvic floor muscle exercises. Currently, BPC-157 therapy has a significant beneficial effect on the condition of these muscles, resulting in a reduced risk of symptom occurrence and their alleviation.

a. BPC-157 peptide therapy

Due to its action profile, BPC-157 peptide acts as a tissue-elasticizing preparation, leading to strengthening of the pelvic floor muscles. As is known from previous articles, the peptide also shows action on the nervous system, which in the case of urinary incontinence results in suppression of the sensation of bladder urgency. BPC-157 peptide therapy, used regularly and preventively, leads to thickening of the muscular structure of the urethra, resulting in a significantly reduced risk of urinary incontinence in the future. Application of BPC-157 therapy leads to complete cure of urinary incontinence.

b. Experimental studies conducted

Female albino rats weighing from 310g to 350g were used as material for the study.

Course of study: The procedure was performed under deep anesthesia using intraperitoneally administered ketamine. Sharp dissection of the endopelvic fascia was performed, resulting in peripheral detachment of the proximal and distal urethra from the anterior vaginal wall and pubic bone. After the procedure, the control group was administered saline solution and a catheter was placed. The study group received BPC-157 peptide for seven days after the procedure. During the study, bladder contractions and resulting leakages were observed by filling the bladder while simultaneously applying pressure to release fluid at the urethral opening. After completion of measurements, the entire bladder and urethra were collected by removing the pubic symphysis, thus preserving the entire urethra segment. Changes within the segment were observed using specialized computer programs connected to a microscope.

Results

BPC-157 peptide therapy, regardless of the dosing regimen or route of administration used, completely counteracts the decrease in LPP values, i.e. intravesical pressure levels. Through the action of BPC-157, original values recorded in healthy rats were achieved. Additionally, the urethral wall treated with BPC-157 shows a thicker and more regular muscular structure, while the control group is characterized by the presence of a thin muscular layer.

Conclusions

The above results indicate that the action of BPC-157 compared to the control has a regenerative effect on urethral damage, and when used during conservative treatment leads to a reduction in the likelihood of urinary incontinence symptoms occurring.

2. Vesicovaginal fistula

A vesicovaginal fistula is a condition very often confused with the aforementioned urinary incontinence. The fistula forms as a result of damage to the thin wall of the bladder, which due to its anatomical structure is located in the vicinity of the vagina. The most common cause of the disease is considered to be a complication following gynecological procedures. Other causes include caesarean section, bladder radiotherapy or endometriosis foci. A vesicovaginal fistula, depending on the size of the canal, can be simple or complex. The symptom of fistula formation is the entry of urine into the vagina, accompanied by abdominal pain, intestinal obstruction and hematuria. In acute and complex cases, treatment is usually surgical. In cases of additional treatment to accelerate regeneration or for preventive purposes, BPC-157 peptide therapy is used.

a. BPC-157 peptide therapy

Based on the studies below, BPC-157 therapy is a safe peptide profile, administered parenterally or orally to people with vesicovaginal fistulas. Under certain conditions, it can be one of the solutions in the process of healing post-fistula wounds. Vesicovaginal fistulas are associated with frequent intimate infections, a feeling of discomfort and gradually exclude patients from social life, which is why the selection of appropriate and safe therapy such as BPC-157 therapy is so important. In the case of additional treatment alongside surgical treatment, BPC-157 participates in the post-operative regeneration of the vesicovaginal fistula. In the case of preventive as well as regenerative treatment, in simple cases, it can prevent the formation and recurrence of this disease as well as treat it.

b. Experimental studies conducted

Material

Female rats weighing 200g, aged 8 to 10 weeks, were used for the study.

Course of study

The procedure was performed under deep anesthesia using intraperitoneally administered ketamine. A longitudinal incision was made in the posterior wall of the bladder and the anterior wall of the vagina over a length of 4 mm, creating a vesicovaginal fistula using a single-layer technique with interrupted sutures. BPC-157 was administered at doses of 10 μg/kg, 1 μg/kg, 100 ng/kg and 10 ng/kg throughout the duration of the experiment, i.e. on day zero when therapy begins, and daily for the duration of the trial over periods of 7, 14, 21, 28 and 42 days. Control animals received an equivalent amount of saline. Immediately before sacrifice of the animals, under deep anesthesia, the fluid pressure required for fistula leakage was measured (biomechanical examination). Differences in fistula healing between groups were observed using microscopic examination. During the study, the possibility of urine presence in the vagina, possible urinary incontinence and the macroscopic appearance of the vagina and urethra were observed daily. After sacrifice of the animals, the presence of adhesions, signs of infection and healing of the fistula tissue on the bladder and vaginal side were observed.

Results

After administration of BPC-157 peptide at all doses (10 μg/kg, 1 μg/kg, 100 ng/kg and 10 ng/kg), particularly 14 days after surgery, the diameter of the fistula opening was significantly reduced. Closure of the vesicovaginal fistula occurred in all rats treated with BPC-157 therapy after a 6-week peptide treatment period. Additionally, the absence of urinary stones was found during the study. In the control group of animals, the presence of urinary stones and a vesicovaginal fistula were found. In the histological image, visible collagenization and neovascularization causing closure of the tissue defect and alleviation of the inflammatory state under the influence of BPC-157 were observed.

Conclusions

Through the action of BPC-157 at doses of 10 μg/kg, 1 μg/kg, 100 ng/kg and 10 ng/kg, healing of the vesicovaginal fistula in rats occurs, indicating that BPC-157 has very strong protective action through alleviating tissue damage and structural abnormalities caused by injury.

3. Ureteral stenosis

Ureteral stenosis, also called ureteropelvic junction obstruction, is a condition involving a defect of the ureter, leading to retention/stasis of urine above the stenosis. The flow of urine to the bladder, produced by the kidneys, is prevented due to improper functioning of the ureter. This process leads to urine retention in the kidney with a simultaneous increase in intrarenal pressure, destruction of renal parenchyma and their failure, resulting in hydronephrosis. The causes of ureteral stenosis include, among other things, congenital defects of the smooth muscles of the ureteral wall, abnormal vascularization of the ureter, connective tissue adhesions or vesicoureteral reflux. Hydronephrosis can appear in one or both kidneys, and depending on this, different symptoms occur. If hydronephrosis affects one kidney, symptoms such as pain in the lumbar region, vomiting and nausea or a positive Goldflam's sign occur. Hydronephrosis in both kidneys is characterized by symptoms such as loss of appetite, weight gain, swelling of both lower limbs or weakness and nausea. When acute symptoms and disease course occur, surgical treatment is indicated. In mild cases, specialized medications and the pioneering BPC-157 therapy can be used in treating ureteral stenosis.

a. BPC-157 therapy

BPC-157 peptide therapy promotes proper action and functioning of the ureter. The flow of urine to the bladder, produced by the kidneys, is enabled through the action of the ureter. Through the action of BPC-157, intrarenal pressure is reduced, which significantly improves kidney condition and their efficiency. Hydronephrosis arising during ureteral stenosis is inhibited or eliminated under the influence of the peptide. In preventive treatment using BPC-157 therapy, it leads to a reduction in the risk of ureteral stenosis developing in the future.

b. Experimental studies conducted

Material Male rats were used in the study.

Course of study:

Ureteral ligation was performed in rats, leading to hydronephrosis, development of fibrosis, tubular cell damage and interstitial inflammation. After the injury was created, BPC-157 peptide at a dose of 10 μg/kg and 10 ng/kg was administered by intraperitoneal injection. In the control group, an equivalent amount of saline was used. Assessment of results was made at 24 and 96 hours after peptide administration and included changes in the kidneys on a scale from 0 to 3, where: 0 – healthy kidney, 1 – mild hydronephrosis, 2 – moderate hydronephrosis, visible dilation of the renal pelvis, few changes on the kidney surface, 3 – severe hydronephrosis, dilation of the renal pelvis, thinning of the renal parenchyma and a significant number of changes on the kidney surface.

Results:

The action of BPC-157 peptide causes clear and advanced improvement in the condition of the ureter, observed at both 24 and 96 hours. Regular, severe hydronephrosis, dilation of the renal pelvis and thinning of the renal parenchyma were inhibited. Acute hydronephrosis was restored to a state of mild hydronephrosis or its complete absence.

Conclusions:

The action of BPC-157 peptide at a dose of 10 μg/kg and 10 ng/kg causes elimination of the hydronephrosis state, increased intrarenal pressure or renal failure, leading to inhibition of ureteral stenosis disease.

4. Scrotal injury

Scrotal injury is a trauma belonging to the group of blunt injuries, i.e. those arising under the influence of bruising, damage caused by occupational work, injuries acquired during accidents, assaults or when practicing selected sports disciplines. Open and closed injuries can be distinguished. Open injuries occur when the continuity of the scrotal skin is disrupted. In the case of damage to the scrotum itself, a skin defect most commonly develops. In closed injuries, swelling, tenderness and bruising may occur. In treatment, in the case of scrotal skin defects, coverage using skin grafts from the perineal or thigh area is possible. In the case of bruising and minor scrotal injuries, regenerative drug therapy is introduced, including BPC-157 peptide therapy.

a. BPC-157 therapy

BPC-157 shows strong, beneficial and regenerating action against developed scrotal swelling, which under the influence of the peptide was significantly alleviated. Regular use of BPC-157 peptide will lead to alleviation of pain and swelling symptoms accompanying scrotal injury. Treatment using BPC-157 is characterized by high effectiveness and safety in its action profile, and additionally prevents the growth and enlargement of scrotal injuries and swelling.

5. Cystitis

Cystitis is defined as a state of urinary tract infection caused by microorganisms present within it, which can multiply, leading to the development of inflammation. Under normal conditions, the urinary tract above the bladder sphincter point is sterile. The bacterial microorganism responsible for the majority of cases of bladder inflammation is Escherichia coli (E. coli). This bacterium can travel from the anus to the urethral opening, then to the bladder with the possibility of entering one or both kidneys. Symptoms accompanying cystitis include pain and burning during urination, frequent urination and pain in the lower abdomen. Additionally, red or dark red coloration of urine may occur, indicating hematuria resulting from inflammation of the bladder mucosa. In the first stage of treatment, oral treatment is used, most commonly through the administration of furazidine. To alleviate symptoms, pain-relieving or antispasmodic agents can additionally be introduced. For more acute complaints and course of cystitis, implementation of an appropriate antibiotic based on an antibiogram is recommended. Currently, BPC-157 peptide therapy is used for cystitis complaints.

a. BPC-157 therapy

The action of BPC-157 peptide shows bacteriostatic action, preventing the multiplication of pathogens. It mobilizes the immune system to fight microorganisms in the urinary tract, which leads to elimination of the inflammatory state in the bladder and cure of its inflammation. Additionally, BPC-157 can be used in preventive treatment for recurrent cystitis, eliminating the development of this condition.

Nephroprotective action of BPC-157

The concept of nephroprotection

Nephroprotection can be understood in two ways. Firstly, this process concerns the protection of the kidneys, both in a disease state – where nephroprotective actions prevent symptom exacerbation – and when they are healthy, through action preventing the development of diseases and conditions. In the understanding relating to the subject of nephrology, nephroprotection concerns the plan of both implementing and withdrawing medications and procedures leading to the protection of healthy kidneys and alleviation of symptoms in diseased kidneys. Focusing on the concept of nephroprotection, we can refer to the action profile of modern BPC-157 peptide therapy. BPC-157 peptide shows nephroprotective action that is both preventive and alleviating.

Nephroprotective BPC-157 therapy

The nephroprotective action of BPC-157 peptide is presented using the example of the toxic effect on the kidneys of cisplatin, a drug used in chemotherapy. While the peptide cannot be used during cancer treatment, the example of how devastating such therapy is for the kidneys can be used to indicate its nephroprotective action. With regard to the action of drugs with a milder degree of action and all types of damage, it will act even more effectively and safely. BPC-157 peptide therapy, showing nephroprotective action, involves reduction of proteinuria while preserving glomerular filtration function as a result of simultaneous dilation of the afferent and efferent arterioles, through which there is no increase in intraglomerular pressure or disturbances in glomerular autoregulation. The totality of the above processes constitutes the nephroprotective action of BPC-157 peptide.

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