**4. Urinary tract infections**

Androgens have been found to increase oxidative stress in the prostate gland [41]. Pathological levels of ROS bring about lipid peroxidation, apoptosis and DNA damage [15]. Lipid peroxi‐ dation is one of the main signs of oxidative damage, and has been found to stimulate alterations in membrane structure and has been linked to enzyme inactivation [41]. ROS cause this by abstracting a hydrogen atom from side chains of fatty acids in the cell membrane, initiating

Intracellular changes in the levels of ROS occur during proliferative, apoptotic and senescent processes, which can lead to the activation of signalling pathways [40]. As mentioned previ‐ ously, changes in tissue oxygenation during these processes causes and upregulation of cytokines and growth factors, which trigger prostatic cell proliferation, prostatic growth and inflammation. These processes themselves are a source of oxidative stress, which then leads to further proliferation and the initiation a chronic inflammation. The presence of ROS is thus an essential component in the pathogenesis of BPH when present at high levels within the prostate. This will help reduce ROS levels to physiologically homeostatic levels, allowing them to carry out their functions as signal transducers without activating any pathological mecha‐

Endogenous antioxidant levels decrease with age [42], and this is compounded by other agerelated changes which ultimately lead to the manifestation of BPH. Oxidative stress can lead to cell mutations, which may lead to carcinogenesis and remodelling of the gland's internal structure [43]. BPH is an alternative, benign pathway of unregulated prostatic growth which is encouraged by inflammatory mediators and increased oxidative stress [41]. Management of

Management of oxidative stress is also an important factor in the prevention and treatment of BPH [41]. Buchu is an antioxidant-rich natural remedy that may be used to reduce oxidative stress. The polyphenolics contained within the plant scavenge free radicals, allowing them to

. The hydrogen donating ability of the phenolic groups1

the bulid up of ROS. By donating hydrogen groups, these polyphenolics will stabilise free

An increase in free radicals stimulates cyclooxygenase(COX) [44], a key enzyme in initiantion of the inflammatory process. Increase COX activity stimulates the production of an array of pro-inflammatory substances called prostaglandins. In patients with BPH and prostatitis there is an increased production of cyclooxygenase 2 (COX-2) and a reduction in the levels of prostaglandin E1 [44]. Free radical scavengers, particularly hydroxyl radical scavengers, suppress the over expression of COX and prostaglandin synthesis [44]. Ethanolis extracts of Buchu (Agathosma betulina) possess an inhibitory effect on COX-2 synthesis [44]. This inhibition will, as a consequence, suppress the inflammatory response and reduce hypertro‐ phy/hyperplasia and inflammation of the prostate, which is the goal of antioxidant treatment.

Reducing levels of ROS allows Buchu to interrupt the pathogenesis of BPH by reducing tissue injury, DNA damage, neoplastic transformation, and activation of growth factors that lead to abnormal cell proliferation and growth [40]. A diet rich in antioxidants such as vitamins A, C and E may also be prescribed to work in unison with Buchu to reduce oxidative stress.

will help reduce

lipid peroxidation which has been found to enhance carcinigenesis [41].

304 Antioxidant-Antidiabetic Agents and Human Health

oxidative stress is thus an imperative step in the management of BPH [41].

radicals, preventing them from attacking nearby cells to acquire it.

nisms.

act as anti-oxidants1

UTI's have a varied incidence that is dependent on age, sex and predisposing factors [45]. UTI's are an uncommon occurrence in healthy young men, but incidence does increase with an increase in age due to predisposing factors and urological abnormalities [45].

The most common cause of UTI'sare bacteria, the most common being Escherichia coli, Klebsiella pneumonia, enterococci and Staphylococcus epidermidis, to name a few [45]. Bacteria causing UTI'sin men have been found to reach the urinary tract via an ascending route [45]. The bacterial flora found around the region of the anus is a reservoir for potential pathogens of the urinary tract [45]. Invasion of the urinary tract is lead by colonisation of the opening of the urethra, followed by adhesion and attachment to the epithelial lining of the urethra, with growth of bacteria on the urethral surface leading to ascension of bacteria into the urinary tract [45]. Invasion of the urethra by bacteria is difficult in men due to the distance between the opening of the urethra and the perianal region where the bacteria causing UTI'sare known to reside, the length of the urethra and the presence of prostatic fluid in the urethra, which is known to have bactericidal activity [45].

Co-infection of the prostate in patients with UTI'sis unknown [45], but a mechanism has been suggested. Reflux of urine into ducts of the prostate lead to the retrograde transfer of bacteria from the urethra into the prostate, bringing about infection of the prostate gland (bacterial prostatitis) [46].

Men with UTI'sare usually predisposed to them by functional or structural abnormalities [47, 49]. Lesions of the urinary tract which predispose men to UTI'sinclude bladder outlet obstruc‐ tion, bladder stones, stricture of the urethra, cancer of the bladder and kidney stones [50].

Signs and symptoms of UTI'sinclude frequency, pain on urination, flank pain and/or costovertebral angle tenderness, which is tenderness in the area overlying the kidney [45].

Lower UTI'sare related to erectile dysfunction and BPH [51]. This interaction may be affected by extraneous variables such as diabetes, aging and coronary artery diseases such as athero‐ sclerosis, but it was found to be independent of these variables when the co-morbidities were controlled for [51]; the association between lower UTI's(UTI) and erectile dysfunction remains. Men who are found to have more severe lower UTI's have more severe erectile dysfunction [51]. The mechanism that gives rise to this interaction is obstruction of the urethra which is propagated by collagen deposition in the penile ultrastructure and the subsequent loss of smooth muscle [2 . The loss of smooth muscle leads to the reduction in erectile tissue, resulting in erectile dysfunction.

Buchu has been found to have antimicrobial activity against bacteria that cause urinary tract infections, i.e. Staphylococcus aureus and Klebsiella pneumonia.

Flavonoids found in buchu may modulate inflammation and strengthen connective tissue. They may be used in the acute and long-term use for chronic or recurrent UTI, reducing the symptoms caused by UTI's [52]. The diuretic actions of Buchu will also assist in the reduction of inflammation by helping to flush bacteria out of the urinary tract through its ability to increase urinary output [52], serving to reduce colonisation of the urethra by bacteria, reducing the duration of the UTI.

way into the seminal plasma, which has been associated with the production of free radicals and a decrease in antioxidant function [15]. Cigarette smoking also increases concentrations of leukocytes in seminal plasma [15]. Excessive intake of alcohol increases ROS while decreas‐ ing antioxidants due to increased ethanol metabolism [60]. Spinal cord injury is associated with higher levels of ROS and higher numbers of leukocytes, both of which are known to contribute to oxidative stress, leading to reduces sperm motility and poor sperm morphology [61, 62]. Dilatation of veins in the plexus surrounding the spermatic cord (varicocele) is associated with increased levels of ROS, with a concomitant decrease in sperm function [63]. Higher quantities of nitric oxide have also been found in men with varicocele, and these men have also been

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http://dx.doi.org/10.5772/57233

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As previously stated, ROS have both physiological and pathological roles. Physiological levels of ROS have been found to play a vital role in normal sperm function [15]. ROS are signalling molecules in many processes which allow fertilisation [15]. ROS are essential in sperm maturation as they have been shown to stabilise sperm chromatin, which is required to maintain genetic integrity [15]. Capacitation, a process which occurs in the female genital tract, is a maturation process which gives sperm the ability to gain hyperactive motility and the potential to carry out an acrosome reaction [15]; both of which are vital for fertilisation to take place. Capacitation is a series of molecular changes that brings about membrane hyperpolarisation, protein phosphorylation and an increase in pH and cAMP [65]. Hyperactivation, a subsection of capacitaion, provide spermatozoa with the ability to move through cervical mucous and to penetrate cumulus cells of the oocyte [15]. The acrosome reaction, which is the release of proteolytic enzymes contained within the acrosomal cap, helps to degrade the extracellular matrix of the zona pellucida [65]. This allows spermatozoa to burrow through the zona pellucida, allowing penetration of this layer to permit fusion with the oocyte. Physiological levels of ROS are also essential for sperm-oocyte fusion [15]. Fluidity of the sperm membrane is required to fusion to take place [66]. This is acquired by spermatozoa through capacitation and acrosome reaction [15], processes which are both assisted by the presence of ROS. Membrane fluidity allows

Pathological levels of ROS are detrimental to sperm function [15]. An imbalance between ROS and antioxidant defence mechanisms results in pathological processes to be initiated. ROS cause damage to proteins, lipid molecules and DNA [67]. Lipid peroxiation causes loss of fatty acids from sperm plasma membranes, which affects the structure and func‐ tion (i.e. fluidity, transport processed, receptor transduction) of spermatozoa, impairing the functional parameters of sperm and their ability to fertilize [67, 68]. Sperm is usually resistant to DNA damage due to the tight packaging of DNA material and the innate antioxidant defense mechanisms in place [69]. ROS causes DNA damage and leads to infertility. Nitric oxide and hydrogen peroxide have been found to induce DNA damage, which brings about DNA fragmentation and reduced sperm parameters (i.e. motility, and morphology) [70, 73]. The impaired the ability of the Y chromosome to repair DNA strand breaks makes spermatozoa more vulnerable to DNA damage [74]. Damage to cellular components initiates apoptosis. Abnormal spermatozoa are regularly removed via program‐

found to have higher markers of oxidative stress [64].

sperm to fuse with the oocyte, allowing successful fertilisation.

Buchu may be used in the form of a herbal tincture or a herbal tea. The tincture will deliver adequate quantities of the herb allowing its actions to be distributed throughout the body. The tea will support the herbal action of the tincture and simultaneously increase fluid intake [52].

Buchu may be used alone or in combination with other plants. In combination, the synergistic interactions of the extracts found in buchu and those of other plants will produce a better therapeutic effect in the treatment of a variety of ailments, or, in this instance, in the treatment of UTI's[44]. Antibiotic resistance is rife, and is the cause of a prolonged disease course. A combination of antimicrobial agents helps prevent resistance to antibiotics, increases the spectrum of activity and may even reduce the side effects of therapy [44]. A combination of the plants Agathosma crenulata, Dodonaea viscose and Eucalyptus globules produces a broad spectrum and enhanced antimicrobial activity [44]. Combination of these plants in a 1:1:1 ratio provides additive and synergistic effects [53] where the extracts of each plant act via multiple mechanisms to reduce the number of disease causing microbials. The mixture of bioactive constituents target numerous target sites and work in a synergistic manner [53]. The combi‐ nation of these plants give an additive anti-inflammatory, anti-fungal, analgesic, antibacterial and antiviral effect [54, 55].

By preventing and reducing colonisation of the urinary tract that leads to urinary tract infections, other co-morbidities associated with UTI's such as erectile dysfunction, prostatitis and erectile dysfunction may be simultaneously prevented.
